Functional and evolutionary analysis of the mouse Muc-1 gene

The mouse homologue of the human tumour-associated mucin, MUC1, was cloned and full-length sequence was determined. This mucin (previously called polymorphic epithelial mucin) is expressed by the majority of simple secretory epithelial cells in both the mouse and human and is also overexpressed in a large percentage of carcinomas. The mouse gene, Muc-1, encodes an integral membrane protein with 44% of its coding capacity made up of serine, threonine and proline, a composition typical of a highly O-glycosylated protein. The Muc-1 core protein consists of an amino-terminal signal sequence, a repetitive domain encoding 16 repeats of 20-21 amino acids, and unique sequence containing membrane-spanning and cytoplasmic domains. Although overall homology with the human MUC1 protein is only 53%, the transmembrane and cytoplasmic domains exhibit homologies of 90% and 87%, respectively. This level of sequence conservation would suggest that these regions may be functionally important. Interestingly, the mouse homologue, unlike its human counterpart does not exhibit a variable number tandem repeat (VNTR) polymorphism. However, this type of polymorphism was found to be present in all other mammalian groups analysed. Data is presented, including sequence obtained for the Muc-1 gene from a large number of species, to suggest how this gene has evolved and to explain possible reasons why the mouse Muc-1 gene does not exhibit minisatellite characteristics. Numerous functions have been suggested for this molecule, yet it still remains unclear what role this protein plays in the tissues and tumours in which it is expressed. In an effort to learn more of the function of the mouse Muc-1 gene, the gene was specifically mutated in embryonic stem (ES) cells. Targeting vectors derived through genomic clones from two strains of mice were utilised and their relative targeting efficiencies are discussed. Several mouse cell lines were created carrying a disruption in the Muc-1 gene. These cell lines were injected into nude mice to create tumours and also injected into blastocysts, in order to generate mice carrying the Muc-1 mutation. These mouse lines will provide a crucial tool in the analysis of the function of this molecule in vivo

Recurrent Breast Cancer Diagnosis Delayed by COVID-19 Pandemic

We describe the case of a 65-year-old female with a history of left-sided ductal carcinoma in situ in 2008. Mammography in January 2020 demonstrated calcifications in the previously affected breast. Subsequent stereotactic biopsy results were benign. In the months that followed, the patient experienced breast changes but avoided returning to the facility as the COVID-19 pandemic worsened. In August of 2020, the patient returned for a repeat mammogram, which indicated 2 suspicious masses in the left breast. Further analysis through ultrasound-guided core biopsy ultimately led to a left mastectomy and lymph node biopsy, which were performed in September 2020. Pathology results revealed multifocal invasive ductal carcinoma stage IIB

Extrapulmonary Tuberculosis: A Case Report Involving the Spine and Soft Tissues

Tuberculosis (TB) is a major health concern worldwide, and its incidence is increasing in developed countries, especially among immigrant populations. Extrapulmonary TB with musculoskeletal involvement is often a difficult and delayed diagnosis, as the disease can mimic metastases or infection. We present a case of extrapulmonary TB affecting the spine and soft tissues of a Vietnamese-born patient living in the United States. We discuss the imaging findings associated with extrapulmonary TB of the spine. Familiarity with key imaging features of disease can lead to early suspicion and detection of the disease as well as timely treatment

Bilateral Popliteal Entrapment Syndrome in a Young Athlete Diagnosed with Ultrasound

Popliteal artery entrapment syndrome (PAES) occurs when the popliteal artery is compressed by abnormally developed or hypertrophied muscles adjacent to the popliteal fossa. When symptomatic, it most frequently presents with leg cramping while walking or running. We describe the case of an 18-year-old female runner presenting with claudication and exercise intolerance. After MRI was non-diagnostic, diagnostic ultrasound demonstrated that she had functional (Type VI) PAES. She subsequently underwent popliteal artery release surgery. Type VI PAES should be considered in young, healthy patients who present with claudication, particularly athletes

Survey evaluations of University of British Columbia residents’ education and attitudes regarding palliative care and physician assisted death

Background: Little prior research has been conducted regarding resident physicians’ opinions on the subject of Physician Assisted Death (PAD), despite past surveys ascertaining the attitudes of practicing physicians towards PAD in Canada. We solicited British Columbia residents’ opinions on the amount of education they receive about palliative care and physician assisted death, and their attitudes towards the implementation of PAD.Methods: We conducted a cross sectional, anonymous online survey with the resident physicians of British Columbia, Canada. Questions included: close-ended questions, graded Likert scale questions, and comments. Results: Among the respondents (n=299, response rate 24%), 44% received ≥5 hours of education in palliative care, 40% received between zero and four hours of education, and 16% reported zero hours. Of all respondents, 75% had received no education about PAD and the majority agreed that there should be more education about palliative care (74%) and PAD (85%). Only 35% of residents felt their program provided them with enough education to make an informed decision about PAD, yet 59% would provide a consenting patient with PAD. Half of the respondents believed PAD would ultimately be provided by palliative care physicians.Interpretation: Residents desire further education about palliative care and PAD. Training programs should consider conducting a thorough needs assessment and implementing structured education to meet this need

Novel Interference Suppression Null Steering Antenna System for High Precision Positioning

The high precision (centimetre accuracy) positioning systems are set to play a key role in revolutionising smart farming, self-driving cars, drone deliveries, heavy machine navigation, etc. With so much at stake the technology also needs protection from an intentional sabotage or denial of service. It is very easy with current satellite-based navigation jammers to disrupt a navigation service. Our proposed technology solves this challenge in a compact and cost-effective way. Compared to normal navigation patch antennas our proposed dual ring antenna offers over 30 dB of protection. Thus, if a patch antenna-based navigation system is disturbed at 1 watt of interference power, it will take 1000 watts to disrupt navigation system working on our proposed system. With the size of only 130 mm ×130 mm and cheap large-scale manufacturing, our proposed antenna is perfectly suitable for applications for safety and prosperity of the smart nation-based living

Curiosity Killed the M-Cat: an Examination of Illicit Drugs and Media

Using mainstream media communication theories, this article outlines different mechanisms by which media can impact on public perceptions of drugs and crime. The media can set the agenda and define public interest; frame issues through selection and salience; indirectly shape individual and community attitudes towards risk and norms; and feed into political debate and decision making. We demonstrate how the media can fulfill each of these roles by examining the so-called Miaow Miaow (Mephedrone) legal high ‘epidemic’, as reported in the United Kingdom news media from 2009-2010. In doing so we illustrate that by contributing to hysteria, exerting pressure for policy change and increasing curiosity in drug use, the media can have a potentially powerful impact on demand for drugs and public perceptions of illicit drugs and drugs policy.Sydney Institute of Criminology; School of Social Sciences at the University of Western Sydne

Amplifying the Heat Shock Response Ameliorates ALS and FTD Pathology in Mouse and Human Models

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are now known as parts of a disease spectrum with common pathological features and genetic causes. However, as both conditions are clinically heterogeneous, patient groups may be phenotypically similar but pathogenically and genetically variable. Despite numerous clinical trials, there remains no effective therapy for these conditions, which, in part, may be due to challenges of therapy development in a heterogeneous patient population. Disruption to protein homeostasis is a key feature of different forms of ALS and FTD. Targeting the endogenous protein chaperone system, the heat shock response (HSR) may, therefore, be a potential therapeutic approach. We conducted a preclinical study of a known pharmacological amplifier of the HSR, called arimoclomol, in mice with a mutation in valosin-containing protein (VCP) which causes both ALS and FTD in patients. We demonstrate that amplification of the HSR ameliorates the ALS/FTD-like phenotype in the spinal cord and brain of mutant VCP mice and prevents neuronal loss, replicating our earlier findings in the SOD1 mouse model of ALS. Moreover, in human cell models, we demonstrate improvements in pathology upon arimoclomol treatment in mutant VCP patient fibroblasts and iPSC-derived motor neurons. Our findings suggest that targeting of the HSR may have therapeutic potential, not only in non-SOD1 ALS, but also for the treatment of FTD

Front Propagation at the Nematic-Isotropic Transition Temperature

We study the gradient flow model for the Landau--de Gennes energy functional for nematic liquid crystals at the nematic-isotropic transition temperature on prototype geometries. We study the dynamic model on a three-dimensional droplet and on a disc with Dirichlet boundary conditions and different types of initial conditions. In the case of a droplet with radial boundary conditions, a large class of physically relevant initial conditions generate dynamic solutions with a well-defined nematic-isotropic interface which propagates according to mean curvature for small times. On a disc, we make a distinction between “planar” and “nonplanar” initial conditions, and “minimal” and “nonminimal” Dirichlet boundary conditions. Planar initial conditions generate solutions with an isotropic core for all times, whereas nonplanar initial conditions generate solutions which escape into the third dimension. Nonminimal boundary conditions generate solutions with boundary layers, and these solutions can either have a largely ordered interior profile or an almost entirely disordered isotropic interior profile. Our examples suggest that while critical points of the Landau--de Gennes energy typically have highly localized disordered-ordered interfaces, the transient dynamics exhibits observable interfaces of potential experimental relevance