INDI-integrated nanobody database for immunoinformatics.

Nanobodies, a subclass of antibodies found in camelids, are versatile molecular binding scaffolds composed of a single polypeptide chain. The small size of nanobodies bestows multiple therapeutic advantages (stability, tumor penetration) with the first therapeutic approval in 2018 cementing the clinical viability of this format. Structured data and sequence information of nanobodies will enable the accelerated clinical development of nanobody-based therapeutics. Though the nanobody sequence and structure data are deposited in the public domain at an accelerating pace, the heterogeneity of sources and lack of standardization hampers reliable harvesting of nanobody information. We address this issue by creating the Integrated Database of Nanobodies for Immunoinformatics (INDI, http://naturalantibody.com/nanobodies). INDI collates nanobodies from all the major public outlets of biological sequences: patents, GenBank, next-generation sequencing repositories, structures and scientific publications. We equip INDI with powerful nanobody-specific sequence and text search facilitating access to >11 million nanobody sequences. INDI should facilitate development of novel nanobody-specific computational protocols helping to deliver on the therapeutic promise of this drug format.

A Deadly Cargo: Gene Repertoire of Cytotoxic Effector Proteins in the Camelidae.

Cytotoxic T cells and natural killer cells can kill target cells based on their expression and release of perforin, granulysin, and granzymes. Genes encoding these molecules have been only poorly annotated in camelids. Based on bioinformatic analyses of genomic resources, sequences corresponding to perforin, granulysin, and granzymes were identified in genomes of camelids and related ungulate species, and annotation of the corresponding genes was performed. A phylogenetic tree was constructed to study evolutionary relationships between the species analyzed. Re-sequencing of all genes in a panel of 10 dromedaries and 10 domestic Bactrian camels allowed analyzing their individual genetic polymorphisms. The data showed that all extant Old World camelids possess functional genes for two pore-forming proteins (PRF1, GNLY) and six granzymes (GZMA, GZMB, GZMH, GZMK, GZMM, and GZMO). All these genes were represented as single copies in the genome except the GZMH gene exhibiting interspecific differences in the number of loci. High protein sequence similarities with other camelid and ungulate species were observed for GZMK and GZMM. The protein variability in dromedaries and Bactrian camels was rather low, except for GNLY and chymotrypsin-like granzymes (GZMB, GZMH).

At the Feet of the Fortress: Analysis of Inka Period (ca. AD 1430-1536) Archaeofaunal Assemblages from Residential Unit 1 (RU1), Pucara de Tilcara (Jujuy, Argentina).

This paper reports the results of a zooarchaeological analysis conducted on the occupation layer of a compound structure (Residential Unit 1) of the Pucara de Tilcara archaeological site (Jujuy Province, northwestern Argentina). Its occupation span extends between the 13th and 15th centuries AD, but evidence diagnostic of the Inka Period (AD 1430-1536) is predominant. Residential Unit 1 was a house-workshop that hosted specialized crafts like metallurgy and lapidary during the Inka Period. It was proposed in previous works that artisans living at Pucara de Tilcara were provisioned with agropastoral products by the Inka administration. This paper aims to test that hypothesis against the zooarchaeological evidence of Residential Unit 1. Three variables were used as proxies for state-sponsored distribution: taxonomic diversity (family and species ranks), and skeletal and age profiles of the predominant zoological family (Camelidae) in the assemblage. The results show a high degree of continuity with the regional record, characterized by a herding-hunting strategy focused on domestic and wild species of Camelidae and a mixed mortality pattern. The skeletal profile shows a strong and negative correlation with the desiccation potential of elements, which could be indicative of local production of chalona. Overall, faunal evidence does not show any sign of centralized distribution.

Synergistic roles of climate warming and human occupation in Patagonian megafaunal extinctions during the Last Deglaciation.

The causes of Late Pleistocene megafaunal extinctions (60,000 to 11,650 years ago, hereafter 60 to 11.65 ka) remain contentious, with major phases coinciding with both human arrival and climate change around the world. The Americas provide a unique opportunity to disentangle these factors as human colonization took place over a narrow time frame (~15 to 14.6 ka) but during contrasting temperature trends across each continent. Unfortunately, limited data sets in South America have so far precluded detailed comparison. We analyze genetic and radiocarbon data from 89 and 71 Patagonian megafaunal bones, respectively, more than doubling the high-quality Pleistocene megafaunal radiocarbon data sets from the region. We identify a narrow megafaunal extinction phase 12,280 ± 110 years ago, some 1 to 3 thousand years after initial human presence in the area. Although humans arrived immediately prior to a cold phase, the Antarctic Cold Reversal stadial, megafaunal extinctions did not occur until the stadial finished and the subsequent warming phase commenced some 1 to 3 thousand years later. The increased resolution provided by the Patagonian material reveals that the sequence of climate and extinction events in North and South America were temporally inverted, but in both cases, megafaunal extinctions did not occur until human presence and climate warming coincided. Overall, metapopulation processes involving subpopulation connectivity on a continental scale appear to have been critical for megafaunal species survival of both climate change and human impacts.