interzone

Fracture callus formation is a dynamic stage of bone activity and repair with precise, spatially localized gene expression. Metastatic breast cancer impairs fracture healing by disrupting bone homeostasis and imparting an altered genomic profile. Previous sequencing techniques such as single-cell RNA and in situ hybridization are limited by missing spatial context and low throughput, respectively. We present a preliminary approach using the Visium CytAssist spatial transcriptomics platform to provide the first spatially intact characterization of genetic expression changes within an orthopedic model of impaired fracture healing...

Systems subject to high-frequency driving exhibit Floquet prethermalization, that is, they heat exponentially slowly on a timescale that is large in the drive frequency, τ_{h}∼exp(ω). Nonetheless, local observables can decay much faster via energy conserving processes, which are expected to cause a rapid decay in the fidelity of an initial state. Here we show instead that the fidelities of eigenstates of the time-averaged Hamiltonian, H_{0}, display an exponentially long lifetime over a wide range of frequencies-even as generic initial states decay rapidly...

Apoptosis occurs during development when a separation of tissues is needed. Synovial joint formation is initiated at the presumptive site (interzone) within a cartilage anlagen, with changes in cellular differentiation leading to cavitation and tissue separation. Apoptosis has been detected in phalangeal joints during development, but its role and regulation have not been defined. Here, we use a mouse model of brachydactyly type A1 (BDA1) with an IhhE95K mutation, to show that a missing middle phalangeal bone is due to the failure of the developing joint to cavitate, associated with reduced apoptosis, and a joint is not formed...

INTRODUCTION: the recent mpox outbreak was considered an international public health emergency. OBJECTIVE: describe the epidemiological and clinical characteristics of mpox in a hospital in the province of Buenos Aires. METHODS: case series study in patients ≥15 years of age in the Dermatology service of the Hospital Interzonal General de Agudos "San Martín" in La Plata between August and November 2022. RESULTS: 10 patients were included...

BACKGROUND: The concept of reverse dynamization involves modifying the mechanical environment surrounding a fracture to influence the healing response. Initially, less rigid stabilization is performed to allow micromotion, encouraging cartilaginous callus formation. This is followed by a conversion to more rigid fixation to prevent the disruption of neovascularization, thereby accelerating bone healing and remodeling. The effect of reverse dynamization in distraction osteogenesis has not been studied, to our knowledge...

Primary aldosteronism is the most common single cause of hypertension and is potentially curable when only one adrenal gland is the culprit. The importance of primary aldosteronism to public health derives from its high prevalence but huge under-diagnosis (estimated to be <1% of all affected individuals), despite the consequences of poor blood pressure control by conventional therapy and enhanced cardiovascular risk. This state of affairs is attributable to the fact that the tools used for diagnosis or treatment are still those that originated in the 1970-1990s...

During anaphase, antiparallel overlapping midzone microtubules elongate and form bundles, contributing to chromosome segregation and the location of contractile ring formation. Midzone microtubules are dynamic in early but not late anaphase; however, the kinetics and mechanisms of stabilization are incompletely understood. Using photoactivation of cells expressing PA-EGFP-α-tubulin we find that immediately after anaphase onset, a single highly dynamic population of midzone microtubules is present; as anaphase progresses, both dynamic and stable populations of midzone microtubules coexist...

The vertebrate appendage comprises three primary segments, the stylopod, zeugopod, and autopod, each separated by joints. The molecular mechanisms governing the specification of joint sites, which define segment lengths and thereby limb architecture, remain largely unknown. Existing literature suggests that reciprocal gradients of Retinoic Acid (RA) and Fibroblast Growth Factor (FGF) signaling define the expression domains of putative segment markers, Meis1, Hoxa11, and Hoxa13. Barx1 is expressed in the presumptive joint sites...

Exploration of the remobilization mechanism of trace metals in estuarine sediments remain challenging because of dynamic hydrochemical conditions. This study integrated a chemical sequential extraction procedure (BCR), the diffusive gradient in thin films (DGT) and high-resolution dialysis techniques, and Visual MINTEQ ver.3.1 to identify the seasonal mobilization characteristics of sediment Zn within a tidal reach, South China. The mobility of sediment Zn based on the BCR procedure contradicted the results of DGT analysis...

In vitro models allow for the study of developmental processes outside of the embryo. To gain access to the cells mediating digit and joint development, we identified a unique property of undifferentiated mesenchyme isolated from the distal early autopod to autonomously re-assemble forming multiple autopod structures including: digits, interdigital tissues, joints, muscles and tendons. Single-cell transcriptomic analysis of these developing structures revealed distinct cell clusters that express canonical markers of distal limb development including: Col2a1 , Col10a1 , and Sp7 (phalanx formation), Thbs2 and Col1a1 (perichondrium), Gdf5 , Wnt5a , and Jun (joint interzone), Aldh1a2 and Msx1 (interdigital tissues), Myod1 (muscle progenitors), Prg4 (articular perichondrium/articular cartilage), and Scx and Tnmd (tenocytes/tendons)...

The origin and differentiation mechanism of articular chondrocytes remain poorly understood. Broadly, the difference in developmental mechanisms of articular and growth-plate cartilage is still less elucidated. Here, we identified that the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) is a crucial regulator of articular, but not growth-plate, chondrocyte differentiation during development. At the early stage of mouse knee development (embryonic day 13.5), NFATc1-expressing cells were mainly located in the flanking region of the joint interzone...

Multiple synostoses syndromes (SYNS) are a group of rare genetic bone disorders characterized by multiple joint fusions. We previously reported an SYNS4-causing GDF6 c.1330T>A (p.Tyr444Asn) mutation, which reduced Noggin-induced GDF6 inhibition and enhanced SMAD1/5/8 signaling. However, the mechanisms by which GDF6 gain-of-function mutation alters joint formation and the comprehensive molecular portraits of SYNS4 remain unclear. Herein, we introduced the p.Tyr443Asn (orthologous to the human GDF6 p.Tyr444Asn) mutation into the mouse Gdf6 locus and performed extensive phenotype analysis, joint development investigation, and transcriptome profiling of Gdf6 p...

Transport systems are crucial in many plant processes, including plant-microbe interactions. Nodule formation and function in legumes involve the expression and regulation of multiple transport proteins, and many are still uncharacterized, particularly for nitrogen transport. Amino acids originating from the nitrogen-fixing process are an essential form of nitrogen for legumes. This work evaluates the role of MtN21 (henceforth MtUMAMIT14), a putative transport system from the MtN21/EamA-like/UMAMIT family, in nodule formation and nitrogen fixation in Medicago truncatula...

INTRODUCTION: Different COVID-19 vaccines were developed in a short time after the beginning of pandemics, reducing mortality, especially in high risk population. This was demonstrated in several studies, mostly retrospective or based in mathematical models. The objective was to compare mortality in inpatients with COVID-19 related to vaccination. METHODS: Longitudinal, prospective, comparative, observational study. Inpatients with COVID-19 diagnosis were included between 17/12/2021 and 23/02/22, in Hospital Nacional Prof...

While prior work has established that articular cartilage arises from Prg4-expressing perichondrial cells, it is not clear how this process is specifically restricted to the perichondrium of synovial joints. We document that the transcription factor Creb5 is necessary to initiate the expression of signaling molecules that both direct the formation of synovial joints and guide perichondrial tissue to form articular cartilage instead of bone. Creb5 promotes the generation of articular chondrocytes from perichondrial precursors in part by inducing expression of signaling molecules that block a Wnt5a autoregulatory loop in the perichondrium...

OBJECTIVES: Fibroblasts in synovium include fibroblast-like synoviocytes (FLS) in the lining and Thy1 + connective-tissue fibroblasts in the sublining. We aimed to investigate their developmental origin and relationship with adult progenitors. METHODS: To discriminate between Gdf5 -lineage cells deriving from the embryonic joint interzone and other Pdgfrα -expressing fibroblasts and progenitors, adult Gdf5-Cre;Tom;Pdgfrα-H2BGFP mice were used and cartilage injury was induced to activate progenitors...

OBJECTIVE: To study the features of functional interzonal integration and its dynamics in infants from 0 to 9 months during prospective observation, taking into account the timing gestation, clinical picture and morphological changes on neurosonography (NSG). MATERIAL AND METHODS: A comprehensive unified examination was carried out in dynamics in 89 infants three times at the age of 3, 6, 9 months and included, in addition to assessing the neurological status, the Denver Developmental Screening Test (DDST), transfontanellar ultrasonography with a vector sensor according to the generally accepted method...

A widely used analytical model to quantitatively assess airborne infection risk is the Wells-Riley model which is limited to complete air mixing in a single zone. However, this assumption tends not to be feasible (or reality) for many situations. This study aimed to extend the Wells-Riley model so that the infection risk can be calculated in spaces where complete mixing is not present. Some more advanced ventilation concepts create either two horizontally divided air zones in spaces as displacement ventilation or the space may be divided into two vertical zones by downward plane jet as in protective-zone ventilation systems...

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) plays a key role in the development and progression of many tumors. We found that in colorectal cancer (CRC) HCT116 cells, the binding of PTHrP to its receptor PTHR type 1 (PTHR1) activates events associated with an aggressive phenotype. In HCT116 cell xenografts, PTHrP modulates the expression of molecular markers linked to tumor progression. Empirical evidence suggests that the Met receptor is involved in the development and evolution of CRC...

The formation of the synovial joint begins with the visible emergence of a stripe of densely packed mesenchymal cells located between distal ends of the developing skeletal anlagen called the interzone. Recently the transcriptome of the early synovial joint was reported. Knowledge about enhancers would complement these data and lead to a better understanding of the control of gene transcription at the onset of joint development. Using ChIP-sequencing we have mapped the H3-signatures H3K27ac and H3K4me1 to locate regulatory elements specific for the interzone and adjacent phalange, respectively...