Mothers and Infants in the Prehistoric Santa Clara Valley: What Stable Isotopes Tell Us about Ancestral Ohlone Weaning Practices

Breast-feeding and weaning are a part of childhood in all human populations, but the exact timing of these milestones varies between groups. As infants incorporate the nutrients from breast milk into their growing bones, chemical evidence is captured in the form of higher stable nitrogen (δ15N) isotope values. This study interprets δ15N values in the bone collagen of children (n = 24) buried at the Yukisma Mound (CA-SCL-38), in Santa Clara County, California. Radiocarbon dates for this site span 2200-250 B.P., but primarily fall during the Late period (740-230 B.P.). In the one probable mother-infant pair available for study, a 2.9 per mil enrichment of δ15N values was observed, consistent with the expected trophic level enrichment of breast-feeding infants. δ15N values of children under seven years old suggest the introduction of weaning foods between 1.5 and 2 years of age, and cessation of breast-feeding by 3 to 3.5 years of age. These results differ from the practices reported in the ethnohistoric literature. This paper includes photos of human remains, taken during excavation at CA-SCL-38 by Ohlone Family Consulting Services, the CRM arm of the Muwekma Ohlone Tribe (which also served as the Most Likely Descendant tribal group for this project). The images were provided to the authors by the tribe, and specific permission was granted to include them in this publication

Rewiring of Aminoacyl-tRNA Synthetase Localization and Interactions in Plants With Extensive Mitochondrial tRNA Gene Loss

The number of tRNAs encoded in plant mitochondrial genomes varies considerably. Ongoing loss of bacterial-like mitochondrial tRNA genes in many lineages necessitates the import of nuclear-encoded counterparts that share little sequence similarity. Because tRNAs are involved in highly specific molecular interactions, this replacement process raises questions about the identity and trafficking of enzymes necessary for the maturation and function of newly imported tRNAs. In particular, the aminoacyl-tRNA synthetases (aaRSs) that charge tRNAs are usually divided into distinct classes that specialize on either organellar (mitochondrial and plastid) or nuclear-encoded (cytosolic) tRNAs. Here, we investigate the evolution of aaRS subcellular localization in a plant lineage (Sileneae) that has experienced extensive and rapid mitochondrial tRNA loss. By analyzing full-length mRNA transcripts (PacBio Iso-Seq), we found predicted retargeting of many ancestrally cytosolic aaRSs to the mitochondrion and confirmed these results with colocalization microscopy assays. However, we also found cases where aaRS localization does not appear to change despite functional tRNA replacement, suggesting evolution of novel interactions and charging relationships. Therefore, the history of repeated tRNA replacement in Sileneae mitochondria reveals that differing constraints on tRNA/aaRS interactions may determine which of these alternative coevolutionary paths is used to maintain organellar translation in plant cells

The effects of thyrotropin-releasing hormone and scopolamine in Alzheimer's disease and normal volunteers

Thyrotropin-releasing hormone (TRH), a neuromodulator and possibly a neurotransmitter in the central nervous system, was shown in a prior study of young normal volunteers to attenuate the memory impairment induced by the anticholinergic drug scopolamine. In the present study, the cognitive, behavioral and physiologic effects of high dose TRH (0.5 mg/kg), both alone and following administration of scopolamine, were examined in 10 Alzheimer's disease (AD) patients (mean age±SD=63.5 years) and 12 older normal volunteers (mean age=64.9±8.8 years). On the day AD subjects received TRH alone, modest but statistically significant improvement from baseline performance was documented on some tests of learning and memory, especially in those with mild dementia severity. In comparing cognitive test performance between the scopolamine alone and scopolamine+TRH conditions, only two test scores were significantly higher in the latter condition. In the group of older volunteers, TRH did not attenuate scopolamine-induced cognitive impairment, contrary to prior findings in a group of younger controls. In fact, older subjects performed worse after receiving scopolamine followed by TRH than after receiving scopolamine alone. In addition, no change from baseline cognitive performance was detected after subjects received TRH alone. These findings raise several questions and speculations on possible age-related changes in the cholinergic system, as well as on the mechanism of the interaction of TRH with the cholinergic system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68371/2/10.1177_026988119200600404.pd

Structure-Guided Directed Evolution of Highly Selective P450-Based Magnetic Resonance Imaging Sensors for Dopamine and Serotonin

New tools that allow dynamic visualization of molecular neural events are important for studying the basis of brain activity and disease. Sensors that permit ligand-sensitive magnetic resonance imaging (MRI) are useful reagents due to the noninvasive nature and good temporal and spatial resolution of MR methods. Paramagnetic metalloproteins can be effective MRI sensors due to the selectivity imparted by the protein active site and the ability to tune protein properties using techniques such as directed evolution. Here, we show that structure-guided directed evolution of the active site of the cytochrome P450‐BM3 heme domain produces highly selective MRI probes with submicromolar affinities for small molecules. We report a new, high‐affinity dopamine sensor as well as the first MRI reporter for serotonin, with which we demonstrate quantification of neurotransmitter release in vitro. We also present a detailed structural analysis of evolved cytochrome P450‐BM3 heme domain lineages to systematically dissect the molecular basis of neurotransmitter binding affinity, selectivity, and enhanced MRI contrast activity in these engineered proteins

Epidemiological aspects of facial trauma in a third level hospital in Mexico

Background: Facial trauma is common in early adulthood and may require complex surgery and even high mortality. Methods: Retrospective, cross-sectional study at the Hospital General de México during the period from January 2018 to December 2021. Patients with a diagnosis of fracture of the facial region, who had a complete clinical record, of any age, were included. Patients who did not comply with the treatment in the hospital unit, with incomplete clinical records, were excluded. Through non-probability sampling, a sample of 156 patients was formed. The descriptive data analysis was carried out by calculating frequencies and percentages for the qualitative variables. For the quantitative variables, measures of central tendency and dispersion were calculated according to the distribution of the variables (mean and standard deviation). for variables with normal distribution and median with interquartile range for variables with non-normal distribution). Results: 156 patients were included, the male sex predominated (89.7%), the age group from 21 to 30 years (35.3%), the injury mechanism of aggression by a third party (54.5%). Facial fractures occurred in the following descending order: orbit (64.7%), zygoma (41.7% n=65), mandibular (23.1% n=36), nasal (22.4% n=35), maxilla (21.8% n=34), NOE (4.5% n=7), Le Fort (3.8% n=6), and palate (3.8% n=6). Within orbital fractures, the most frequently affected region was the orbital floor (42.3%). The patients with orbital fracture were mostly men (88.1% versus 11.9%). The highest frequency of these fractures was between the ages of 21 and 30 (38.6%). Surgical treatment of fractures in general was established in 44.9%, performing open reduction and internal fixation of fractures in 41.0%. Conclusions: The most frequent facial fractures are: orbit, zygoma, and mandibular; they mainly affect the male sex in the second decade of life, they are produced mainly by aggressions to third parties. The management of facial fractures is predominantly surgical, through open reduction and internal fixation

Roadmaps to Utopia: Tales of the Smart City

Notions of the Smart City are pervasive in urban development discourses. Various frameworks for the development of smart cities, often conceptualized as roadmaps, make a number of implicit claims about how smart city projects proceed but the legitimacy of those claims is unclear. This paper begins to address this gap in knowledge. We explore the development of a smart transport application, MotionMap, in the context of a £16M smart city programme taking place in Milton Keynes, UK. We examine how the idealized smart city narrative was locally inflected, and discuss the differences between the narrative and the processes and outcomes observed in Milton Keynes. The research shows that the vision of data-driven efficiency outlined in the roadmaps is not universally compelling, and that different approaches to the sensing and optimization of urban flows have potential for empowering or disempowering different actors. Roadmaps tend to emphasize the importance of delivering quick practical results. However, the benefits observed in Milton Keynes did not come from quick technical fixes but from a smart city narrative that reinforced existing city branding, mobilizing a growing network of actors towards the development of a smart region. Further research is needed to investigate this and other smart city developments, the significance of different smart city narratives, and how power relationships are reinforced and constructed through them

Fortilin potentiates the peroxidase activity of Peroxiredoxin-1 and protects against alcohol-induced liver damage in mice

Fortilin, a pro-survival molecule, inhibits p53-induced apoptosis by binding to the sequence-specific DNA-binding domain of the tumor suppressor protein and preventing it from transcriptionally activating Bax. Intriguingly, fortilin protects cells against ROS-induced cell death, independent of p53. The signaling pathway through which fortilin protects cells against ROS-induced cell death, however, is unknown. Here we report that fortilin physically interacts with the antioxidant enzyme peroxiredoxin-1 (PRX1), protects it from proteasome-mediated degradation, and keeps it enzymatically active by blocking its deactivating phosphorylation by Mst1, a serine/threonine kinase. At the whole animal level, the liver-specific overexpression of fortilin reduced PRX1 phosphorylation in the liver, enhanced PRX1 activity, and protected the transgenic animals against alcohol-induced, ROS-mediated, liver damage. These data suggest the presence of a novel oxidative-stress-handling pathway where the anti-p53 molecule fortilin augments the peroxidase PRX1 by protecting it against degradation and inactivation of the enzyme. Fortilin-PRX1 interaction in the liver could be clinically exploited further to prevent acute alcohol-induced liver damage in humans

GSK3-mediated raptor phosphorylation supports amino acid-dependent Q2 mTORC1-directed signalling

The mammalian or mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a ubiquitously expressed multimeric protein kinase complex that integrates nutrient and growth factor signals for the co-ordinated regulation of cellular metabolism and cell growth. Herein, we demonstrate that suppressing the cellular activity of glycogen synthase kinase-3 (GSK3), by use of pharmacological inhibitors or shRNA-mediated gene silencing, results in substantial reduction in amino acid (AA)-regulated mTORC1-directed signalling, as assessed by phosphorylation of multiple downstream mTORC1 targets. We show that GSK3 regulates mTORC1 activity through its ability to phosphorylate the mTOR-associated scaffold protein raptor (regulatory-associated protein of mTOR) on Ser(859). We further demonstrate that either GSK3 inhibition or expression of a S859A mutated raptor leads to reduced interaction between mTOR and raptor and under these circumstances, irrespective of AA availability, there is a consequential loss in phosphorylation of mTOR substrates, such as p70S6K1 (ribosomal S6 kinase 1) and uncoordinated-51-like kinase (ULK1), which results in increased autophagic flux and reduced cellular proliferation