Collective Action and Decision Making: An Analysis of Economic Modeling and Environmental Free-Riding

It is hypothesized that tool-assisted excavation of plant underground storage organs (USOs) played an adaptive role in hominin evolution and was also once considered a uniquely human behavior. Recent data indicate that savanna chimpanzees also use tools to excavate edible USOs. However, those chimpanzees remain largely unhabituated and we lack direct observations of this behavior in the wild. To fill this gap in our knowledge of hominoid USO extractive foraging, we conducted tool-mediated excavation experiments with captive chimpanzees naive to this behavior. We presented the chimpanzees with the opportunity to use tools in order to excavate artificially-placed underground foods in their naturally forested outdoor enclosure. No guidance or demonstration was given to the chimpanzees at any time. The chimpanzees used tools spontaneously in order to excavate the underground foods. They exhibited six different tool use behaviors in the context of excavation: probe, perforate, dig, pound, enlarge and shovel. However, they still excavated manually more often than they did with tools. Chimpanzees were selective in their choice of tools that we provided, preferring longer tools for excavation. They also obtained their own tools mainly from naturally occurring vegetation and transported them to the excavation site. They reused some tools throughout the study. Our new data provide a direction for the study of variables relevant to modeling USO extractive foraging by early hominins.Funding Agencies|La Caixa Foundation Spain [LCF/BQ/EU15/10350002]; University of Oslo, Department of Biosciences, Norway</p

Shape analysis of the StW 578 calotte from Jacovec Cavern, Gauteng (South Africa)

The fossiliferous deposits within the lower-lying Jacovec Cavern in the locality of Sterkfontein yielded valuable hominin remains, including the StW 578 specimen. Because StW 578 mainly preserves the calotte, the taxonomic status of this specimen has been a matter of discussion. Within this context, here we employed high-resolution microtomography and a landmark-free registration method to explore taxonomically diagnostic features in the external surface of the StW 578 calotte. Our comparative sample included adult humans and common chimpanzees as well as one Australopithecus africanus specimen (Sts 5). We partially restored the StW 578 calotte digitally and compared it to extant specimens and Sts 5 using a landmark-free registration based on smooth and invertible surface deformation. Our comparative shape analysis reveals morphological differences with extant humans, especially in the frontal bones, and with extant chimpanzees, as well as intriguing specificities in the morphology of the StW 578 parietal bones. Lastly, our study suggests morphological proximity between StW 578 and Sts 5. Given the intimate relationship between the brain and the braincase, as well as the integration of the hominin face and neurocranium, we suggest that cranial vault shape differences between StW 578 and extant humans, if confirmed by further analyses, could be either explained by differences in brain surface morphology or in the face. Besides providing additional information about the morphology of the Jacovec calotte that will be useful in future taxonomic discussion, this study introduces a new protocol for the landmark-free analysis of fossil hominin cranial shape.Significance:• We provide further information on the enigmatic fossil specimen StW 578.• We introduce a new approach for the morphological study of fossil hominin crania.• We highlight morphological similarities between StW 578 and ‘Mrs Ples’

The atlas of StW 573 and the late emergence of human-like head mobility and brain metabolism

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.The DST-NRF for sponsoring the Micro-XCT facility at Necsa, and the DST-NRF and Wits University for funding the microfocus X-ray CT facility in the ESI. The Ghent University Special Research Fund (BOF-UGent) for the financial support of the Centre of Expertise UGCT (BOF.EXP.2017.0007), the Sterkfontein excavations and MicroCT scanning work have been provided by National Research Foundation and by PAST.http://www.nature.com/srepam2021Anatom

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer’s dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for LBD and detected the known structural variants at the C9orf72 and MAPT loci as associated with FTD/ALS. We also identified rare pathogenic structural variants in both LBD and FTD/ALS. Finally, we assembled a catalog of structural variants that can be mined for new insights into the pathogenesis of these understudied forms of dementia