Biology subjects

Storch, S.

Publications and source records attributed to Storch, S..

3 recordsLinked to original sources

bioRxiv2023

Life and death in Trypillia times: Interdisciplinary analyses of the exceptional human remains from the settlement of Kosenivka, Ukraine (3700-3600 BCE)

We present an interdisciplinary analysis of finds from the Trypillia settlement of Kosenivka, Ukraine (ca. 3700-3600 BCE, Trypillia C1), that links information on human, faunal, and botanical remains with archaeological data to provide exceptionally detailed insights into life and death at a Trypillia mega-site. We obtained osteological, palaeopathological, and histotaphonomic data from human bone fragments; performed carbon and nitrogen stable isotopic analysis of human and animal bone to calculate food webs with the software FRUITS; and modelled newly generated radiocarbon dates to refine the sites chronology. The biological profile of seven identified individuals, some of whom suffered from disease symptoms common in the Chalcolithic, represents a demographic cross-section of the population. The analysis of perimortem cranial trauma suffered by two individuals suggest cases of interpersonal conflict. Food web calculations demonstrate the large contribution of cereals to the protein component of the human diet, which is supported by dental observations, and we suggest that livestock were a major manure producer for crop cultivation. The most probable scenario for the formation of the Kosenivka find assemblage is a deathly fire event. This makes the site a rare example where the archaeological and osteological results can be used to reconstruct a minimum number of house inhabitants. Following a literature review, we contextualise our analysis by discussing the general lack of human remains from Early and Middle Trypillia sites. The individuals from Kosenivka form part of the less than 0.05% of the total estimated Trypillia population that is represented skeletally; its members were deposited within settlements in the Middle Trypillia stage (until C1), preceding the shift to extramural burials in its late phase (C2). Our detailed results indicate the huge explanatory potential that has yet to be unlocked in the rare and often poorly preserved bioarchaeological archives of the Cucuteni-Trypillia phenomenon.

evolutionary biology↗

bioRxiv2022

CLN7 mutation causes aberrant redistribution of protein isoforms and contributes to Batten disease pathobiology

The variant late infantile form of the inherited neurodegenerative Batten disease (BD) is caused by mutations in the CLN7/MFSD8 gene and represents a strong candidate for gene therapy. Post-natal intracerebral administration of AAV9-hCLN7 to Cln7{Delta}ex2 knockout mice resulted in extended lifespan but dose escalation resulted in reduced acuity in neurophysiology tests, cerebral atrophy and elevated neuroinflammation. Comparing patient and control iPSC-derived neural progenitor cells (iNPC) we discovered that CLN7 localizes to the nucleus as well as the endolysosomal network and is differentially distributed in BD iNPC. Proteomics identified a profound nuclear defect in BD iNPC that compounds with mitochondrial and lysosomal metabolic defects resulting in elevated apoptosis. We further identified a 50kDa common nuclear CLN7 isoform and a 37kDa isoform that accumulates only in BD iNPC nuclei. Our findings suggest that successful treatment of CLN7 BD will require combinatorial therapies addressing both loss and aberrant gain of protein function.

cell biology↗

bioRxiv2020

Mitochondrial collapse links PFKFB3-promoted glycolysis with CLN7/MFSD8 neuronal ceroid lipofuscinosis pathogenesis

The neuronal ceroid lipofuscinoses (NCLs) are a family of monogenic life-limiting pediatric neurodegenerative disorders collectively known as Batten disease1. Although genetically heterogeneous2, NCLs share several clinical symptoms and pathological hallmarks such as lysosomal accumulation of lipofuscin and astrogliosis2,3. CLN7 disease belongs to a group of NCLs that present in late infancy4-6 and, whereas CLN7/MFSD8 gene is known to encode a lysosomal membrane glycoprotein4,7-9, the biochemical processes affected by CLN7-loss of function are unexplored thus preventing development of potential treatments1,10. Here, we found in the Cln7{Delta}ex2 mouse model11 of CLN7 disease that failure in the autophagy-lysosomal pathway causes accumulation of structurally and bioenergetically impaired, reactive oxygen species (ROS)-producing neuronal mitochondria that contribute to CLN7 pathogenesis. Cln7{Delta}ex2 neurons exhibit a metabolic shift mediated by pro-glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3). PFKFB3 inhibition in Cln7{Delta}ex2 mice in vivo and in CLN7 patients-derived cells rectified key disease hallmarks. Thus, specifically targeting glycolysis may alleviate CLN7 pathogenesis.

neuroscience↗