Age is an essential trait for understanding the ecology and management of wildlife. A conventional method of estimating age in wild animals is counting annuli formed in the cementum of teeth. This method has been used in bears despite some disadvantages, such as high invasiveness and the requirement for experienced observers. In this study, we established a novel age estimation method based on DNA methylation levels using blood collected from 49 brown bears of known ages living in both captivity and the wild. We performed bisulfite pyrosequencing and obtained methylation levels at 39 cytosine-phosphate-guanine (CpG) sites adjacent to 12 genes. The methylation levels of CpGs adjacent to four genes showed a significant correlation with age. The best model was based on DNA methylation levels at just four CpG sites adjacent to a single gene, SLC12A5, and it had high accuracy with a mean absolute error of 1.3 years and median absolute error of 1.0 year after leave-one-out cross-validation. This model represents the first epigenetic method of age estimation in brown bears, which provides benefits over tooth-based methods, including high accuracy, less invasiveness, and a simple procedure. Our model has the potential for application to other bear species, which will greatly improve ecological research, conservation, and management.

Internet of Things (IOT) related and IOT enabled education and research are becoming more prevalent in today’s academic environment. One of the challenges faced by educators and researchers is the availability of resources to support lab based, hands on learning and research projects. Existing resources are often highly customized, balkanized, and difficult to manage. For new technology areas such as IOT, these environments rarely provide opportunities for resource sharing and interdisciplinary collaboration. In this paper we describe the development of a multi-tenant, IOT centric platform, the Environmental Sensing Data Network (ESDN) meant to support plug and play sensor deployment and the tools necessary for data management. The platform turns the University campus into an open platform that can be used to easily set up IOT based labs for education, research, campus infrastructure management and community applications innovation. The paper covers the development of a sensor augmentation module facilitating easy deployment and management. The operational tools and services integration are also described. We believe the platform is an important step in facilitating distance and in person education and research. ESDN is rapidly expanding beyond the multi-site University campus supporting a growing number of research and community projects.

In the last two decades, an increasing number of bacterial species have been recognized that are able to generate a phenotypically diverse population that shares an identical genotype. This ability is dependent on a complex genetic regulatory network that includes cellular and environmental signals, as well as stochastic elements. Among Bacilli, a broadly distributed family of Rap (Response-regulator aspartyl phosphate) phosphatases is known to modulate the function of the main phenotypic heterogeneity regulators by controlling their phosphorylation. Even more, their related extracellular Phr (Phosphatase regulator) peptides function as quorum sensing signals, creating a cell-cell communication network that regulates the phenotypic development of the entire population. In this review, we examine the role that the Rap phosphatases and their Phr peptides play in the regulation of B. subtilis phenotypic differentiation, and in other members of the Bacillus genus. We also highlight the contribution of these regulatory elements to the fitness of bacterial cells and mobile genetic elements, e.g. prophages and conjugative vectors.

Alveolar bone exostoses (ABE) are benign localized convex outgrowths of buccal or lingual bone from the cortical plate, often known as buttress bone development. Our review and case series shows ABE following orthodontic treatment. If self-remission fails after orthodontic forces are removed, we have shown surgical methods to correct ABE

Several approaches can correct pseudo Class III anterior crossbite. 2x4 appliance, compressed open coil springs, Class III elastics, etc. All cause either soft tissue lacerations, smile line flattening or upper incisor overproclination.This paper describes a novel method to tip lower incisors into a normal overjet without compromising the upper dentition

Foot and ankle TB is rarest form of skeletal TB. It's symptoms may present slowly over an extended period of time, making a diagnosis difficult. For the best outcome and to reduce the risk of deformity diagnosis must be early. The treatment is 12 months rifampin-based regimen for drug-susceptible TB.

Interactions between invaders and resource availability may explain variation in their success or management efficacy. For widespread invaders, regional variation in plant response to nutrients can reflect phenotypic plasticity of the invader, genetic structure of invading populations, or a combination of the two. The wetland weed Alternanthera philoxeroides (alligatorweed) is established throughout the southeastern USA and California, and has high genetic diversity despite primarily spreading clonally. Despite its history in the USA, the role of genetic variation for invasion and management success is only now being uncovered. To better understand how nutrients and genotype may influence A. philoxeroides invasion, we measured the response of plants from 26 A. philoxeroides populations (three cp haplotypes) to combinations of nitrogen (4 or 200 mg/L N) and phosphorus (0.4 or 40 mg/L P). We measured productivity (biomass accumulation and allocation), plant architecture (stem diameter and thickness, branching intensity) and foliar traits (toughness, dry matter content, percent N, percent P). A short-term developmental assay was also conducted by feeding a subset of plants from the nutrient experiment to the biological control agent Agasicles hygrophila, to determine whether increased availability of N or P to its host influenced agent performance, as has been previously suggested. A. philoxeroides haplotype Ap1 was more plastic than other haplotypes in response to nutrient amendments, producing more than double the biomass from low to high N and 50-68% higher shoot:root ratio than other haplotypes in the high N treatment. A. philoxeroides haplotypes differed in 7 of 10 variables in response to increased N. We found no differences in short-term A. hygrophila development between haplotypes but mass was 23% greater in high than low N treatments. This study is the first to explore the interplay between nutrient availability, genetic variation, and phenotypic plasticity in invasive characteristics of the global invader, A. philoxeroides.

The field of food allergy has seen tremendous change over the past 5-10 years with seminal studies redefining our approach to prevention and management and novel testing modalities in the horizon. Early introduction of allergenic foods is now recommended, challenging the previous paradigm of restrictive avoidance. The management of food allergy has shifted from a passive avoidance approach to active interventions that aim to provide protection from accidental exposures, decrease allergic reaction severity and improve the quality of life of food-allergic patients and their families. Additionally, novel diagnostic tools are making their way into the clinical practice with the goal to reduce the need for food challenges and assist physicians in the -- often complex -- diagnostic process. With all the new developments and available choices for diagnosis, prevention and therapy, shared decision-making has become a key part of the medical consultation, enabling patients to make the right choice for them, based on their values and preferences. Communication with patients has also become more complex over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context. The role of the allergist has evolved to embrace all the above exciting developments and provide patients with the optimal care that fits their needs. In this review, we discuss recent developments, as well as the evolution of the field of food allergy in the next decade.

Complex PTSD (CPTSD) is a new diagnosis in the World Health Organization (WHO)’s International Classification of Diseases (ICD-11). This case study describes the delivery of Skills Training in Affective and Interpersonal Regulation and Narrative Therapy (SNT), a flexible, multi-component therapy that addresses the symptoms of CPTSD. SNT balances interventions that address current day stressors with those that reappraise the meaning of traumatic past events. This paper outlines 16 sessions of SNT with a 55-year-old gay man. The treatment introduces client tailored coping skills for current minority stress, discrimination and micro-aggressions as well as trauma-focused interventions regarding events from his childhood and the death of his partner and many members of his community due to the AIDS epidemic. Qualitative and quantitative outcomes are summarized. Implications regarding the relevance of SNT for sexual and gender minority (SGM) individuals is discussed.

In recent years, health care providers have seen an increase in the number of patients with difficult-to-treat wounds and burns. The bio polymer-based wound dressing shields the injured part and aids in the recapture of epithelial and dermal tissues throughout the process of healing. The total count of a person with chronic lesions has been expanding whole due to developing society, over weight and cardiovascular illness. The development of ideal wound dressing material with excellent characteristics like antimicrobial activity, biocompatibility, free radical scavenging capacity, non-adherent property, the hydrophilicity of alginate, cellulose, chitosan, collagen has an increasing demand for the treatment of chronic wounds. Nevertheless, owing to the above mention property, natural polymers are being used for several key functions of biomedicine like narcotic distribution systems, tissue manufacturing, bandages etc. accordingly, the significance of these bio-based polymers interfered with healing functions that lead to inform and inspire youth and scientist researchers worldwide to grab with these far-reaching areas of medicine and biology. The review highlights the physiochemical property of natural polymer, biological evaluation of various materials as wound dress, along with their synthesis and mechanical properties, clinical status, challenges and future perspectives.

A large part of the soil protist diversity is missed in metabarcoding studies based on 0.25 g of soil environmental DNA (eDNA) and universal primers due to ca. 80 % co-amplification of non-target plants, animals and fungi. To overcome this problem, enrichment of the substrate used for eDNA extraction is an easyly implemented option but its effect has not yet been tested. In this study, we evaluated the effect of a 150 µm mesh size filtration and sedimentation method to improve the recovery of protist eDNA, while reducing the co-extraction of plant, animal and fungal eDNA, using a set of contrasted forest and alpine soils from La Réunion, Japan, Spain and Switzerland. Biodiversity of the whole eukaryotic community was estimated with V4 18S rRNA metabarcoding and classical amplicon sequence variant calling. A 2-3-fold enrichment in shelled protists (Euglyphida, Arcellinida and Chrysophyceae) was observed at the sample level with the proposed method, with, at the same time, a 2-fold depletion of Fungi and a 3-fold depletion of Embryophyceae. Protist alpha diversity was slightly lower in filtered samples due to reduced coverage in Variosea and Sarcomonadea, but significant differences were observed in only one region. Beta diversity was mostly impacted by region and habitat, and explained the same variance in bulk soil and filtered samples. The increase resolution in the soil protist diversity provided by the filtration-sedimentation method is a strong argument to include it in the standard preparation of any future soil for protist eDNA metabarcoding studies.

Background: Pain is the clinical hallmark of sickle cell disease (SCD) leading to hospitalization, psychological sequelae and a decreased health-related quality of life. The aim of this systematic literature review is to evaluate the efficacy of non-pharmacological interventions in reducing sickle cell-related pain in children with SCD. Methods: A comprehensive literature search up until October 2022 was performed to identify studies that investigated the efficacy of non-pharmacological interventions on (1) pain frequency and/or intensity, and (2) analgesic and health service use in children with SCD. Randomized controlled (RCTs) trials and quasi-experimental designed (QED) studies that investigated non-pharmacological interventions for pediatric patients with SCD until the age of 21 years were considered for inclusion. Results: Ten articles (5 RCTs and 5 QED studies) with 422 participants were included. They investigated cognitive behavioral therapy (CBT) (n =5), biofeedback (n=2), massage (n=1), virtual reality (n=1) and yoga (n=1). CBT, biofeedback, massage, virtual reality and yoga significantly reduced frequency and/or intensity of SCD-related pain. Biofeedback also significantly reduced analgesic use. Conclusion: Non-pharmacological interventions may be effective in reducing pain in pediatric SCD patients. However, due to the heterogeneity of the included studies a quantitative analysis could not be performed. Awaiting further supporting evidence, healthcare providers should consider implementing these interventions as valuable part of a comprehensive pain management strategy plan to improve the outcome of sickle cell-related pain.

Biofilms can increase pathogenic contamination of drinking water, cause biofilm-related diseases, alter the sediment erosion rate, and degrade contaminants in wastewater. Compared with mature biofilms, biofilms in the early-stage have been shown to be more susceptible to antimicrobials and easier to remove. Mechanistic understanding of physical factors controlling early-stage biofilm growth is critical to predict and control biofilm development, yet such understanding is currently incomplete. Here, we reveal the impacts of hydrodynamic conditions and microscale surface roughness on the development of early-stage Pseudomonas putida biofilm through a combination of microfluidic experiments, numerical simulations, and fluid mechanics theories. We demonstrate that early-stage biofilm growth is suppressed under high flow conditions and that the critical local velocity for early-stage P. putida biofilms to develop is about 50 μm/s, similar to P. putida’s swimming speed. We further illustrate that microscale surface roughness promotes the growth of early-stage biofilms by increasing the area of the low-flow region. Furthermore, we show that the critical average shear stress, above which early-stage biofilms cease to form, is 0.9 Pa for rough surfaces, three times as large as the value for flat or smooth surfaces (0.3 Pa). The important control of flow conditions and microscale surface roughness on early-stage biofilm development, characterized in this study, will facilitate future predictions and managements of early-stage P. putida biofilm development on the surfaces of drinking water pipelines, blood vessels, and sediments in aquatic environments.

Cuproptosis, the current form of regulated cell death characterized by copper overload, oligomerization of lipoacylated proteins, and loss of the Fe-S cluster proteins, has been proposed to function closely with human diseases including cancer. Since the first identification in 2022, a wide range of strategies have been developed to induce cuproptosis for cancer therapy, such as small-molecule drugs and nanomaterials. Although many reviews related to cuproptosis have been reported, they remain at a basic mechanism level and a summary covering recent progress in the field of nanotechnologies in cuproptosis-based cancer therapy has not yet been presented. Therefore, it is time to fill the gap and shed light on future directions for the application of this promising tool to fight against cancer. In this minireview, we first expounded the mechanism of action of cuproptosis and emphasized the feasibility of triggering cuproptosis for cancer therapy. The recent progress of cancer treatments based on nanoparticle-induced cuproptosis was then described. Finally, the challenges and future development directions of the emerging field of cuproptosis were also discussed.

BJOG-22-0767.R1 Multimorbidity warrants a proactive management of pregnancy in cancer survivors

Cas13 are the only CRISPR/Cas systems found so far, which target RNA strand while preserving chromosomal integrity. Cas13b or Cas13d cleaves RNA by the crRNA guidance. However, the effect of the characteristics of the spacer sequences, such as the length and sequence preference, on the activity of Cas13b and Cas13d remains unclear. Our study shows that neither Cas13b nor Cas13d has a particular preference for the sequence composition of gRNA, including the sequence of crRNA and its flanking sites on target RNA. However, the crRNA, complementary to the middle part of the target RNA, seems to show higher cleavage efficiency for both Cas13b and Cas13d. As for the length of crRNAs, the most appropriate crRNA length for Cas13b is 22-25 nt and crRNA as short as 15 nt is still functional. Whereas, Cas13d requires longer crRNA, and 22-30 nt crRNA can achieve good effect. Both Cas13b and Cas13d show the ability to process precursor crRNAs. Our study suggests that Cas13b may have a stronger precursor processing ability than Cas13d. There are few in vivo studies on the application of Cas13b or Cas13d in mammals. With the methods of transgenic mice and hydrodynamic injection via tail vein, our study showed that both of them had high knock-down efficiency against target RNA in vivo. These results indicate that Cas13b and Cas13d have great potential for in vivo RNA operation and disease treatment without damaging genomic DNA.

VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest known adhesion G protein-coupled receptor. Mutations in VLGR1/ADGRV1 cause Usher syndrome (USH), the most common form of hereditary deaf-blindness, and have been additionally linked to epilepsy. Although VLGR1/ADGRV1 is almost ubiquitously expressed, little is known about the subcellular function and signalling of the VLGR1 protein and thus about mechanisms underlying the development of diseases. Using affinity proteomics, we have identified key components of autophagosomes as putative interacting proteins of VLGR1. In addition, whole transcriptome sequencing of the retinae of the Vlgr1/del7TM mouse model revealed altered expression profiles of gene-related autophagy. Monitoring autophagy by immunoblotting and immunocytochemistry of the LC3 and p62 as autophagy marker proteins revealed evoked autophagy in VLGR1-deficient hTERT-RPE1 cells and USH2C patient-derived fibroblasts. Our data demonstrate the molecular and functional interaction of VLGR1 with key components of the autophagy process and point to an essential role of VLGR1 in the regulation of autophagy at internal membranes. The close association of VLGR1 with autophagy helps to explain the pathomechanisms underlying human USH and epilepsy-related to VLGR1 defects.

VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest adhesion G protein-coupled receptor aGPCRs. Mutations in VLGR1/ADGRV1 are associated with human Usher syndrome (USH), the most common form of deaf-blindness, and also with epilepsy in humans and in mice. Although VLGR1 is almost ubiquitously expressed in CNS and ocular and inner ear sensory cells. Little is known about the pathogenesis of the diseases related to VLGR1. We previously identified VLGR1 as a vital component of focal adhesions (FA) serving as a metabotropic mechanoreceptor that controls cell spreading and migration. FAs are highly dynamic and turnover frequently in response to internal and external signals. Here, we aimed to elucidate how VLGR1 participates in FA turnover. Nocodazole washout assays and live-cell imaging of RFP-paxillin consistently demonstrated that FA disassembly was not altered, de novo assembly of FA was significantly delayed in Vlgr1-deficient astrocytes indicating that VLGR1 is enrolled in the assembly of FAs. In FRAP experiments recovery rates were significantly reduced in Vlgr1-deficient FAs, indicating reduced turnover kinetics in VLGR1-deficient FAs. We showed that VLGR1 regulates cell migration by controlling the FA turnover during their assembly. From this, we expect novel insights into pathomechanisms related to pathogenic dysfunctions of VLGR1.