The archaeological visibility of chimpanzee (Pan troglodytes) nut-cracking.

The earliest evidence for complex tool use in the archaeological record dates to 3.3 Ma. While wooden tools may have been used by our earliest ancestors, the evidence is absent due to poor preservation. However, insights into possible early hominin wooden tool use can be gained from observing the tool-use practices of our closest living relatives, chimpanzees (Pan troglodytes). By using stone hammers used to crack various nuts, chimpanzees leave a durable material signature comprised of formal tools and associated diagnostic fragments. While the archaeological evidence of chimpanzee wooden tool use is temporary, the combination of stone hammers and wooden anvils can create a more enduring lithic record. This study explores the lithic assemblages associated with wooden and stone anvil use at nut-cracking sites in Taï National Park, Côte d'Ivoire, using technological and use-wear analyses. Our results indicate clear differences in density, fracture patterns, and use-wear in the lithic records between wooden anvil and stone anvil sites. New archaeological excavations at six chimpanzee nut-cracking sites reveal that the anvils' material directly influences the visibility of nut-cracking evidence in the archaeological record. By examining the nature of the lithic signatures associated with wooden anvil and stone anvil use by chimpanzees, we can formulate hypotheses about the probability of such behaviors being preserved and identifiable in the Plio-Pleistocene hominin archaeological record. The variability in material signatures from nut-cracking on different anvils suggests that stone anvils leave a clear archaeological record. Evidence for wooden anvil use is likely underrepresented due to the more ephemeral nature of the associated percussive damage and material signature. It may, however, still be possible, albeit challenging, to identify wooden anvil use in the archaeological record.

New Oldowan locality Sare-Abururu (ca. 1.7 Ma) provides evidence of diverse hominin behaviors on the Homa Peninsula, Kenya.

The Homa Peninsula, in southwestern Kenya, continues to yield insights into Oldowan hominin landscape behaviors. The Late Pliocene locality of Nyayanga (∼3-2.6 Ma) preserves some of the oldest Oldowan tools. At the Early Pleistocene locality of Kanjera South (∼2 Ma) toolmakers procured a diversity of raw materials from over 10 km away and strategically reduced them in a grassland-dominated ecosystem. Here, we report findings from Sare-Abururu, a younger (∼1.7 Ma) Oldowan locality approximately 12 km southeast of Kanjera South and 18 km east of Nyayanga. Sare-Abururu has yielded 1754 artifacts in relatively undisturbed low-energy silts and sands. Stable isotopic analysis of pedogenic carbonates suggests that hominin activities were carried out in a grassland-dominated setting with similar vegetation structure as documented at Kanjera South. The composition of a nearby paleo-conglomerate indicates that high-quality stone raw materials were locally abundant. Toolmakers at Sare-Abururu produced angular fragments from quartz pebbles, representing a considerable contrast to the strategies used to reduce high quality raw materials at Kanjera South. Although lithic reduction at Sare-Abururu was technologically simple, toolmakers proficiently produced cutting edges, made few mistakes and exhibited a mastery of platform management, demonstrating that expedient technical strategies do not necessarily indicate a lack of skill or suitable raw materials. Lithic procurement and reduction patterns on the Homa Peninsula appear to reflect variation in local resource contexts rather than large-scale evolutionary changes in mobility, energy budget, or toolmaker cognition.

Simulation and social network analysis provide insight into the acquisition of tool behaviour in hybrid macaques.

The pathways through which primates acquire skills are a central focus of cultural evolution studies. The roles of social and genetic inheritance processes in skill acquisition are often confounded by environmental factors. Hybrid macaques from Koram Island (Thailand) provide an opportunity to examine the roles of inheritance and social learning to skill acquisition within a single ecological setting. These hybrids are a cross between tool-using Burmese long-tailed (Macaca fascicularis aurea) and non-tool-using common long-tailed macaques (Macaca fascicularis fascicularis). This population provides an opportunity to explore the roles of social learning and inheritance processes while being able to exclude underlying ecological factors. Here, we investigate the roles of social learning and inheritance in tool use prevalence within this population using social network analysis and simulation. Agent-based modelling (ABM) is used to generate expectations for how social/asocial learning and inheritance structure the patterning in a social network. The results of the simulation show that various transmission mechanisms can be differentiated based on associations between individuals in a social network. The results provide an investigative framework for discussing tool use transmission pathways in the Koram social network. By combining ABM, network analysis, and behavioural data from the field we can investigate the roles social learning and inheritance play in tool acquisition of wild primates.

Modeling Oldowan tool transport from a primate perspective.

Living nonhuman primates have long served as a referential framework for understanding various aspects of hominin biological and cultural evolution. Comparing the cognitive, social, and ecological contexts of nonhuman primate and hominin tool use has allowed researchers to identify key adaptations relevant to the evolution of hominin behavior. Although the Oldowan is often considered to be a major evolutionary milestone, it has been argued that the Oldowan is rather an extension of behaviors already present in the ape lineage. This is based on the fact that while apes move tools through repeated, unplanned, short-distance transport bouts, they produce material patterning often associated with long-distance transport, planning, and foresight in the Oldowan. Nevertheless, remain fundamental differences in how Oldowan core and flake technology and nonhuman primate tools are used. The goal of the Oldowan hominins is to produce sharp-edged flakes, whereas nonhuman primates use stone tools primarily as percussors. Here, we present an agent-based model that investigates the explanatory power of the ape tool transport model in light of these differences. The model simulates the formation of the Oldowan record under the conditions of an accumulated short-distance transport pattern, as seen in extant chimpanzees. Our results show that while ape tool transport can account for some of the variation observed in the archaeological record, factors related to use-life duration severely limit how far an Oldowan core can be moved through repeated short-distance transport bouts. Thus, the ape tool transport has limitations in its ability to explain patterns in the Oldowan. These results provide a basis for discussing adaptive processes that would have facilitated the development of the Oldowan.

Did Early Pleistocene hominins control hammer strike angles when making stone tools?

In the study of Early Pleistocene stone artifacts, researchers have made considerable progress in reconstructing the technical decisions of hominins by examining various aspects of lithic technology, such as reduction sequences, hammer selection, platform preparation, core management, and raw material selection. By comparison, our understanding of the ways in which Early Pleistocene hominins controlled the delivery and application of percussive force during flaking remains limited. In this study, we focus on a key aspect of force delivery in stone knapping, namely the hammerstone striking angle (or the angle of blow), which has been shown to play a significant role in determining the knapping outcome. Using a dataset consists of 12 Early Pleistocene flake assemblages dated from 1.95 Ma to 1.4 Ma, we examined temporal patterns of the hammer striking angle by quantifying the bulb angle, a property of the flake's Hertzian cone that reflects the hammer striking angle used in flake production. We further included a Middle Paleolithic flake assemblage as a point of comparison from a later time period. In the Early Pleistocene dataset, we observed an increased association between the bulb angle and other flake variables related to flake size over time, a pattern similarly found in the Middle Paleolithic assemblage. These findings suggest that, towards the Oldowan-Acheulean transition, hominins began to systematically adjust the hammer striking angle in accordance with platform variables to detach flakes of different sizes more effectively, implying the development of a more comprehensive understanding of the role of the angle of blow in flake formation by ∼1.5 Ma.

Practical Synthesis of Terminal Vinyl Fluorides.

The synthesis of di- and trisubstituted vinyl fluorides with high isomeric purity remains a challenge for organic synthesis. While many methods exist to access these compounds, the separation of the desired isomer from the minor isomer and/or starting materials often is difficult. Herein, we report a practical method to access di- and trisubstituted vinyl fluorides via a selective Horner-Wadsworth-Emmons olefination/hydrolysis, which provides crystalline 2-fluoroacrylic acids in high (>98%) E-isomeric purity. A subsequent silver-catalyzed stereoretentive decarboxylation provides the title substances with high isomeric purity and without the need for tedious chromatography to remove the minor isomer. The process was amenable to a variety of aldehydes and ketones and provided a diverse array of di- and trisubstituted vinyl fluorides. The sequence was applied to the synthesis of antibacterial and anti-inflammatory compounds.

Synthesis of beta-site amyloid precursor protein-cleaving enzyme 1 inhibitors BI 1147560 and BI 1181181 labeled with carbon-14 and deuterium.

The generation of amyloid beta peptides that aggregate in the brain is believed to play a major role in Alzheimer's disease. In theory, the inhibition of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), which catalyzes the initial rate-limiting step in amyloid beta production, may slow or stop Alzheimer's disease. Herein, we report the preparation of two potent BACE1 inhibitors, BI 1147560 (1) and BI 1181181 (2), labeled with carbon-14 and with deuterium. The use of advanced key chiral intermediates like 3 and 5 shortened the carbon-14 syntheses of these two compounds to five and six steps, respectively, and helped in preparing them with very high chemical purity and enantiomeric excess without deviating from the process chemistry route. For the deuterium synthesis, oxetan-3-ylmethanamine [2 H6 ]-7 and 2-fluoro-2-methylpropan-1-amine [2 H6 ]-9 were prepared then used with the chiral intermediate 5 to furnish deuterium labeled 1 and 2, respectively.

Childhood Overweight and Obesity and Pubertal Onset Among Mexican-American Boys and Girls in the CHAMACOS Longitudinal Study.

Secular trends in earlier initiation of puberty have been observed in recent decades. One risk factor appears to be increases in adiposity, as measured by body mass index. This trend is particularly notable among Latino populations, who have higher rates of overweight/obesity compared with non-Latino White youth. Previous research has focused primarily on White girls, resulting in data gaps regarding male puberty and among potentially high-risk populations. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, we examined body mass index at age 5 years (2005-2006) and multiple markers of pubertal onset, assessed repeatedly and longitudinally at 7 in-person visits, starting at age 9 and continuing through age 14 (2009-2015), among 336 Mexican Americans in Salinas, California. We observed no associations among boys, but found significantly earlier thelarche in overweight (HR = 1.7, 95% CI: 1.1, 2.7) and obese girls (HR = 1.5, 95% CI: 1.0, 2.4), menarche in overweight girls (HR = 1.6; CI: 1.0, 2.4), and pubarche in obese girls (HR = 1.9; CI: 1.2, 3.0), compared with normal-weight girls. This study examined an understudied population and included key covariates, such as birth weight and early adverse events, which are typically omitted in studies.

Earliest known Oldowan artifacts at >2.58 Ma from Ledi-Geraru, Ethiopia, highlight early technological diversity.

The manufacture of flaked stone artifacts represents a major milestone in the technology of the human lineage. Although the earliest production of primitive stone tools, predating the genus Homo and emphasizing percussive activities, has been reported at 3.3 million years ago (Ma) from Lomekwi, Kenya, the systematic production of sharp-edged stone tools is unknown before the 2.58-2.55 Ma Oldowan assemblages from Gona, Ethiopia. The organized production of Oldowan stone artifacts is part of a suite of characteristics that is often associated with the adaptive grade shift linked to the genus Homo Recent discoveries from Ledi-Geraru (LG), Ethiopia, place the first occurrence of Homo ∼250 thousand years earlier than the Oldowan at Gona. Here, we describe a substantial assemblage of systematically flaked stone tools excavated in situ from a stratigraphically constrained context [Bokol Dora 1, (BD 1) hereafter] at LG bracketed between 2.61 and 2.58 Ma. Although perhaps more primitive in some respects, quantitative analysis suggests the BD 1 assemblage fits more closely with the variability previously described for the Oldowan than with the earlier Lomekwian or with stone tools produced by modern nonhuman primates. These differences suggest that hominin technology is distinctly different from generalized tool use that may be a shared feature of much of the primate lineage. The BD 1 assemblage, near the origin of our genus, provides a link between behavioral adaptations-in the form of flaked stone artifacts-and the biological evolution of our ancestors.

Ecological perspectives on technological diversity at Kanjera South.

The aspects of hominin behavior responsible for Oldowan stone tool variation are the focus of much debate. There is some consensus that this variation arises from a combination of ecological and cultural factors. The diversity of raw material types and technological strategies present at Kanjera South, Kenya, provide an opportunity to examine the interacting influences of ecology and culture on Oldowan stone tool variation. Here, we combine previous analyses of raw material properties, provenance, and technology with quantitative measures of core reduction intensity and tool utilization to examine the influence of both ecological and technocultural factors on stone tool variation at Kanjera South. The results of this analysis reflect a dynamic relationship between raw material properties, provenance, and hominin mobility. Exotic raw materials are generally more resistant to edge attrition compared with those available locally, which may have incentivized their transport over long distances and more extensive reduction. Cores produced on raw materials from distant sources also exhibit more complex core reduction strategies than locally acquired materials. While this pattern is partially due to the differences in the quality of knappable stone, bifacial centripetal and multifacial core reduction strategies also arise due to the continuous transport and use of exotic raw materials. Moreover, the variation in stone tool reduction is not consistent with neutral models of stone tool transport and discard. These results demonstrate that ecological factors such as raw material provenance and physical properties have strong impacts on reduction intensity and the technological strategies used by hominins.

An Examination of Idiographic Networks of Posttraumatic Stress Disorder Symptoms.

Although the application of network theory to posttraumatic stress disorder (PTSD) has yielded promising insights, the lack of equivalence between inter- and intraindividual variation limits the generalizability of these findings to any one individual with PTSD. Instead, a better understanding of how PTSD symptoms occur and vary over time within an individual requires exploring the idiographic network structure of PTSD. To do so, the present study used an intensive repeated-measures design to estimate intraindividual networks of PTSD symptoms on a person-by-person basis. Participants were 20 individuals who met criteria for PTSD and completed daily surveys assessing PTSD symptoms; surveys were completed four times per day for approximately 30 days. Employing a recently validated method provided by Fisher, Reeves, Lawyer, Medaglia, and Rubel (2017), we used these data to estimate a contemporaneous and temporal network of PTSD symptoms for individuals on a person-by-person basis. We then calculated centrality metrics to determine the relative importance of each symptom in each idiographic network. Across all contemporaneous networks, negative trauma-related cognitions and emotions were most commonly the most central symptoms. Further, across all temporal networks, (a) negative trauma-related emotions were the most common driver of variation in other symptoms over time and (b) distressing trauma-related dreams and sleep disturbance were the most common downstream consequences of variation in other PTSD symptoms over time. We also reviewed data from two randomly selected participants to illustrate how this approach could be used to identify maintenance factors of PTSD for each individual and guide individual treatment planning.

Pleistocene animal communities of a 1.5 million-year-old lake margin grassland and their relationship to Homo erectus paleoecology.

The ecological and selective forces that sparked the emergence of Homo's adaptive strategy remain poorly understood. New fossil and archaeological finds call into question previous interpretations of the grade shift that drove our ancestors' evolutionary split from the australopiths. Furthermore, issues of taphonomy and scale have limited reconstructions of the hominin habitats and faunal communities that define the environmental context of these behavioral changes. The multiple ∼1.5 Ma track surfaces from the Okote Member of the Koobi Fora Formation at East Turkana provide unique windows for examining hominin interactions with the paleoenvironment and associated faunas at high spatiotemporal resolution. These surfaces preserve the tracks of many animals, including cf. Homo erectus. Here, we examine the structure of the animal community that inhabited this landscape, considering effects of preservation bias by comparing the composition of the track assemblage to a skeletal assemblage from the same time and place. We find that the track and skeletal assemblages are similar in their representation of the vertebrate paleocommunity, with comparable levels of taxonomic richness and diversity. Evenness (equitability of the number of individuals per taxon) differs between the two assemblages due to the very different circumstances of body fossil versus track preservation. Both samples represent diverse groups of taxa including numerous water-dependent species, consistent with geological interpretations of the track site environments. Comparisons of these assemblages also show a pattern of non-random hominin association with a marginal lacustrine habitat relative to other vertebrates in the track assemblage. This evidence is consistent with behavior that included access to aquatic foods and possibly hunting by H. erectus in lake margins/edaphic grasslands. Such behaviors may signal the emergence of the adaptative strategies that define our genus.

Potent and selective CC chemokine receptor 1 antagonists labeled with carbon-13, carbon-14, and tritium.

1-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (2-methanesulfonyl-pyridin-4-ylmethyl)-amide (1) and its analogs (2) and (3) are potent CCR1 antagonists intended for the treatment of rheumatoid arthritis. The detailed syntheses of these 3 compounds labeled with carbon-13 as well as the preparation of (1) and (2) labeled with carbon-14, and (1) labeled with tritium, are described.

1,4-Dicarbofunctionalization of 4-Fluoroaryl Grignard and Lithium Reagents with Disubstituted Malononitriles.

An efficient one-pot 1,4-dicarbofunctionalization of 4-fluoroaryl Grignard or lithium reagents with 2,2-disubstituted malononitriles is described. The reaction proceeds by sequential transnitrilation and SNAr reactions. Commercial Grignard solutions, Grignard reagents prepared in situ by halogen/magnesium exchange with i-PrMgCl, or aryllithium reagents prepared in situ by bromine/lithium exchange with n-BuLi are compatible with the reaction conditions. Moreover, 2,2-disubstituted malononitriles of diverse structures are accommodated. The reaction provides a unique approach to 1,4-dicarbofunctionalization of activated arenes in a tandem, one-pot transformation.

Rhodium-Catalyzed Addition of Aryl Boronic Acids to 2,2-Disubstituted Malononitriles.

ß-Ketonitriles bearing a quaternary carbon at the 2-position were prepared through Rh-catalyzed addition of aryl boronic acids to 2,2-disubstituted malononitriles. In contrast to the previously described transnitrilative cyanation of aryl boronic acids with dialkylmalononitriles, the present reaction avoids retro-Thorpe collapse of the intermediate addition product through the use of a milder base. The reaction was amenable to a variety of aryl boronic acids and disubstituted malononitriles, providing a diverse array of ß-ketonitriles. The products could be further derivatized to valuable chiral α,α-disubstituted-ß-aminonitriles through addition reactions to the corresponding N-tert-butanesulfinyl imines.

An Enantioselective Synthesis of an 11-ß-HSD-1 Inhibitor via an Asymmetric Methallylation Catalyzed by (S)-3,3'-F2-BINOL.

An efficient asymmetric synthesis of 11-ß-HSD inhibitor 1 has been accomplished in five linear steps and 53% overall yield, starting from the readily available 3-chloro-1-phenylpropan-1-one. The key feature of the synthesis includes an asymmetric methallylation of 3-chloro-1-phenylpropan-1-one catalyzed by the highly effective organocatalyst (S)-3,3'-F2-BINOL under solvent-free and metal-free conditions.

Rhodium-Catalyzed Transnitrilation of Aryl Boronic Acids with Dimethylmalononitrile.

An efficient transnitrilation of aryl boronic acids with dimethylmalononitrile (DMMN) is described. This rhodium-catalyzed electrophilic cyanation presents a novel approach to prepare aryl nitriles by using a carbon-bound cyanating reagent which undergoes cross-coupling with the aryl boronic acid. The reaction expands the degree of functional-group compatibility exhibited by the transnitrilation of aryl Grignard and aryllithium reagents. A variety of aryl boronic acid derivatives and dialkylmalononitriles were amenable to the transnitrilation.

Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis.

An electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides, by a transnitrilation with dimethylmalononitrile (DMMN) was developed. DMMN is a commercially available, bench-stable solid. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates. The transnitrilation of aryllithium species generated by directed ortho-lithiation enabled a net C-H cyanation. The intermediacy of a Thorpe-type imine adduct in the reaction was supported by isolation of the corresponding ketone from the quenched reaction. Computational studies supported the energetic favorability of retro-Thorpe fragmentation of the imine adduct.

Synthesis of two potent glucocorticoid receptor agonists labeled with carbon-14 and stable isotopes.

Two potent glucocorticoid receptor agonists were prepared labeled with carbon-14 and with stable isotopes to perform drug metabolism, pharmacokinetics, and bioanalytical studies. Carbon-14 labeled (1) was obtained from an enantiopure alkyne (5) via a Sonogashira coupling to a previously reported 5-amino-4-iodo-[2-(14)C]pyrimidine [(14)C]-(6), followed by a base-mediated cyclization (1) in 72% overall radiochemical yield. Carbon-14 labeled (2) was prepared in five steps employing a key benzoic acid intermediate [(14)C]-(13), which was synthesized in one pot from enolization of trifluoromethylketone (12), followed by bromine-magnesium exchange and then electrophile trapping reaction with [(14)C]-carbon dioxide. A chiral auxiliary (S)-1-(4-methoxyphenyl)ethylamine was then coupled to this acid to give [(14)C]-(15). Propargylation and separation of diastereoisomers by crystallizations gave the desired diastereomer [(14)C]-(17) in 34% yield. Sonogashira coupling to iodopyridine (10) followed by cyclization to the azaindole [(14)C]-(18) and finally removal of the chiral auxiliary gave [(14)C]-(2) in 7% overall yield. For stable isotope syntheses, [(13)C6]-(1) was obtained in three steps using [(13)C4]-(6) and trimethylsilylacetylene-[(13)C2] in 26% yield, while [(2)H5]-(2) was obtained by first preparing the iodopyridine [(2)H5]-(10) in five steps. Then, Sonogashira coupling to chiral alkyne (24) and cyclization gave [(2)H5]-(2) in 42% overall yield.