Which types of bony changes in the maxillary sinus indicate chronic sinusitis?

Objectives: To determine which types of bone lesion (spicules, lobules, porous bone) in the maxillary sinus indicate sinusitis METHODS: Subadjacent dental disease is a cause of maxillary sinusitis; if a lesion type indicates sinusitis it should be more common above diseased posterior maxillary teeth than a lesion type that is not indicative of sinusitis. The study sample is a British Mediaeval human skeletal collection.

Results: Porous bone lesions (chiefly new bone deposits) in maxillary sinuses are associated with subadjacent dental disease; spicules/lobules of bone in the sinus are not.

The palaeopathology of industry, a perspective from Britain.

Objectives: This article considers the position of palaeopathology of ca. 1750AD onward within the subdiscipline of Industrial Archaeology, and reflects upon the relationship between skeletal palaeopathology and textual sources on disease prevalences.

Methods: It draws upon the author's experience in engaging with threat-led archaeology.

Toxic effects of mutant huntingtin in axons are mediated by its proline-rich domain.

Huntington's disease results from expansion of a polyglutamine tract (polyQ) in mutant huntingtin (mHTT) protein, but mechanisms underlying polyQ expansion-mediated toxic gain-of-mHTT function remain elusive. Here, deletion and antibody-based experiments revealed that a proline-rich domain (PRD) adjacent to the polyQ tract is necessary for mHTT to inhibit fast axonal transport and promote axonal pathology in cultured mammalian neurons. Further, polypeptides corresponding to subregions of the PRD sufficed to elicit the toxic effect on fast axonal transport, which was mediated by c-Jun N-terminal kinases (JNKs) and involved PRD binding to one or more SH3-domain containing proteins.

The nuclear receptor LRH-1 discriminates between ligands using distinct allosteric signaling circuits.

Nuclear receptors (NRs) are transcription factors that regulate essential biological processes in response to cognate ligands. An important part of NR function involves ligand-induced conformational changes that recruit coregulator proteins to the activation function surface (AFS), ~15 Å away from the ligand-binding pocket. Ligands must communicate with the AFS to recruit appropriate coregulators and elicit different transcriptional outcomes, but this communication is poorly understood.

Ligand dependent interaction between PC-TP and PPARδ mitigates diet-induced hepatic steatosis in male mice.

Phosphatidylcholine transfer protein (PC-TP; synonym StarD2) is a soluble lipid-binding protein that transports phosphatidylcholine (PC) between cellular membranes. To better understand the protective metabolic effects associated with hepatic PC-TP, we generated a hepatocyte-specific PC-TP knockdown (L-Pctp) in male mice, which gains less weight and accumulates less liver fat compared to wild-type mice when challenged with a high-fat diet. Hepatic deletion of PC-TP also reduced adipose tissue mass and decreases levels of triglycerides and phospholipids in skeletal muscle, liver and plasma.

The nuclear receptor LRH-1 discriminates between ligands using distinct allosteric signaling circuits.

Nuclear receptors (NRs) are transcription factors that regulate essential biological processes in response to cognate ligands. An important part of NR function involves ligand-induced conformational changes that recruit coregulator proteins to the activation function surface (AFS), ~15 Å away from the ligand binding pocket. Ligands must communicate with the AFS to recruit appropriate coregulators and elicit different transcriptional outcomes, but this communication is poorly understood.

A phospholipid mimetic targeting LRH-1 ameliorates colitis.

Phospholipids are ligands for nuclear hormone receptors (NRs) that regulate transcriptional programs relevant to normal physiology and disease. Here, we demonstrate that mimicking phospholipid-NR interactions is a robust strategy to improve agonists of liver receptor homolog-1 (LRH-1), a therapeutic target for colitis. Conventional LRH-1 modulators only partially occupy the binding pocket, leaving vacant a region important for phospholipid binding and allostery.

Is dietary deficiency of calcium a factor in rickets? Use of current evidence for our understanding of the disease in the past.

Objective: Rickets is considered an indicator of vitamin D deficiency in palaeopathology, but a strand of biomedical thought maintains that dietary calcium deficiency may sometimes play a part in its causation. Our aim is to evaluate the extent to which low calcium intake should be considered as a factor in biocultural interpretations of rickets.

Methods: We assess published modern epidemiological studies that provide primary data to support claims for a role for dietary calcium deficiency in rickets.

Direct foam writing in microgravity.

Herein we report 2D printing in microgravity of aqueous-based foams containing metal oxide nanoparticles. Such hierarchical foams have potential space applications, for example for in situ habitat repair work, or for UV shielding. Foam line patterns of a TiO-containing foam have been printed onto glass substrates via Direct Foam Writing (DFW) under microgravity conditions through a parabolic aircraft flight.

A content analysis by bibliometry of the first ten years of the International Journal of Paleopathology.

Objectives: The aim is to provide an overview of the nature of the content of palaeopathology articles in the International Journal of Paleopathology during the first ten years of publication (2011-2020), and to compare these results with those from other similar journals.

Methods: The method used is bibliometry of International Journal of Paleopathology plus nine other periodicals publishing in the field of osteoarchaeology / palaeopathology. In these ten journals, 2513 publications in human osteology are reviewed of which 1032 are devoted specifically or substantially to palaeopathology.

MYCOBACTERIA IN SKIN LESIONS AND THE HABITAT OF THE ENDANGERED HOUSTON TOAD (ANAXYRUS HOUSTONENSIS).

Head-starting of the federally endangered Houston toad (Anaxyrus houstonensis), that is, the release of egg strands, tadpoles, and metamorphic juveniles produced in captivity into the original breeding ponds, requires assessment of potential threats for the transmission of pathogens from captive to free-ranging toads. We used Illumina-based 16S rRNA V3 amplicon sequencing to investigate the community structure of bacteria from skin lesions of captive Houston toad and habitat (pond) samples. Proteobacteria, alone or together with Actinobacteria and, in some samples, Cyanobacteria represented virtually all reads in tissue lesion samples, whereas pond samples were much more diverse, with Acidobacteria, Actinobacteria, Bacteriodetes, Chloroflexi, Cyanobacteria, Firmicutes, Planctomycetes, Proteobacteria, and Verrucomicrobia present with little variation between samples.

Empowering MYC carcinogenesis via RNA loops.

Cieśla et al. (2021) uncover intricate circuits of post-transcriptional regulation induced by the Myc oncogene, including alternative splicing and translational control, which are relevant for breast cancer prognosis and contribute to metabolic reprogramming and stem cell-like features of cancer cells.

Quantifying cortical bone in fragmentary archeological second metacarpals.

Objectives: Skeletal variation in cortical bone thickness is an indicator of bone quality and health in archeological populations. Second metacarpal radiogrammetry, which measures cortical thickness at the shaft midpoint, is traditionally used to evaluate bone loss in bioarcheological and some clinical contexts. However fragmentary elements are regularly omitted because the midpoint cannot be determined.

Enantiomer-specific activities of an LRH-1 and SF-1 dual agonist.

Chirality is an important consideration in drug development: it can influence recognition of the intended target, pharmacokinetics, and off-target effects. Here, we investigate how chirality affects the activity and mechanism of action of RJW100, a racemic agonist of the nuclear receptors liver receptor homolog-1 (LRH-1) and steroidogenic factor-1 (SF-1). LRH-1 and SF-1 modulators are highly sought as treatments for metabolic and neoplastic diseases, and RJW100 has one of the few scaffolds shown to activate them.

Atomic-Level Mechanism of Pre-mRNA Splicing in Health and Disease.

Intron removal from premature-mRNA (pre-mRNA splicing) is an essential part of gene expression and regulation that is required for the production of mature, protein-coding mRNA. The spliceosome (SPL), a majestic machine composed of five small nuclear RNAs and hundreds of proteins, behaves as an eminent transcriptome tailor, efficiently performing splicing as a protein-directed metallo-ribozyme. To select and excise long and diverse intronic sequences with single-nucleotide precision, the SPL undergoes a continuous compositional and conformational remodeling, forming eight distinct complexes throughout each splicing cycle.

A dual process model for paleopathological diagnosis.

Objectives: This paper aims to provide an explicit theoretical model for the cognitive processes involved in paleopathological diagnosis.

Methods: The approach adopted is a dual process model (DPM). DPMs recognize that cognition is a result of both Type 1 (intuitive) and Type 2 (analytical) processes.

Development of a new class of liver receptor homolog-1 (LRH-1) agonists by photoredox conjugate addition.

LRH-1 is a nuclear receptor that regulates lipid metabolism and homeostasis, making it an attractive target for the treatment of diabetes and non-alcoholic fatty liver disease. Building on recent structural information about ligand binding from our labs, we have designed a series of new LRH-1 agonists that further engage LRH-1 through added polar interactions. While the current synthetic approach to this scaffold has, in large part, allowed for decoration of the agonist core, significant variation of the bridgehead substituent is mechanistically precluded.

A new approach to recording nasal fracture in skeletonized individuals.

Objective: This work describes a new method for recording nasal fracture in skeletonized individuals, suitable for use in biocultural studies of violence and fracture in past societies.

Methods: The method consists in recording the 'side of fracture', 'side of deviation', 'type of fracture', 'other facial fractures', and stage of 'bone remodeling'.

Results: A lateral impact force to the facial area is typical of interpersonal violence.

Development of a Versatile and Sensitive Direct Ligand Binding Assay for Human NR5A Nuclear Receptors.

As regulators of steroidogenesis, development, and metabolism, the nuclear receptor 5A (NR5A) subfamily members steroidogenic factor 1 (SF-1) and liver receptor homologue 1 (LRH-1) are important pharmacological targets for cancers and metabolic diseases. Evaluation of small molecule modulators and candidate endogenous ligands for these orphan receptors has been hindered by the lack of accessible, robust direct-binding assays. Here, we leverage the potency of our new NR5A agonist (6N) to create a high-affinity probe for fluorescence polarization competition assays by conjugating 6N to fluorescein (FAM).

Dynamic respiratory muscle function in late-onset Pompe disease.

Maximal inspiratory pressure (PI) reflects inspiratory weakness in late-onset Pompe disease (LOPD). However, static pressure tests may not reveal specific respiratory muscle adaptations to disruptions in breathing. We hypothesized that dynamic respiratory muscle functional tests reflect distinct ventilatory compensations in LOPD.

Development of the First Low Nanomolar Liver Receptor Homolog-1 Agonist through Structure-guided Design.

As a key regulator of metabolism and inflammation, the orphan nuclear hormone receptor, liver receptor homolog-1 (LRH-1), has potential as a therapeutic target for diabetes, nonalcoholic fatty liver disease, and inflammatory bowel diseases (IBD). Discovery of LRH-1 modulators has been difficult, in part due to the tendency for synthetic compounds to bind unpredictably within the lipophilic binding pocket. Using a structure-guided approach, we exploited a newly discovered polar interaction to lock agonists in a consistent orientation.