The discovery of a ten-generation m.C1494T pedigree in the east of England with probable links to King Richard III.

This paper reports the discovery of a m.C1494T pedigree in the east of England made during a search for matrilineal relations of King Richard III. The mitochondrial DNA variant m.

Humanin P3S, haplogroup N1b and the risk of Alzheimer's disease.

A commentary of the paper 'Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4-induced brain pathology' that appeared recently in Aging Cell. The possible association of a mitochondrial haplogroup with a disease is frequently discussed. The Humanin peptide encoded by the mtDNA has been shown to play an important regulatory role in cell metabolism.

Diverse retinal-kidney phenotypes associated with homozygous whole-gene deletions in patients with kidney failure.

Unlabelled: A precise diagnosis in medicine allows appropriate disease-specific management. Kidney failure of unknown aetiology remains a frequent diagnostic label within the haemodialysis unit and kidney transplant clinic, accounting for 15-20% of these patients. Approximately 10% of such cases may have an underlying monogenic cause of kidney failure.

Pleomorphic dermal sarcoma: Clinicopathological features and outcomes from a 5-year tertiary referral centre experience.

Background: Pleomorphic dermal sarcoma (PDS) describes rare dermal-based malignant tumours that are morphologically similar to atypical fibroxanthoma (AFX). PDS may be differentiated from AFX by the presence of one or more of the following histologic features: subcutaneous invasion, tumour necrosis, lymphovascular invasion (LVI), and/or perineural infiltration (PNI).

Aims: To further define the clinicopathological features, surgical management, and outcomes of PDS primary tumours.

Necrotic plaques in an elderly male.

Reactive perforating collagenosis is commonly recognised as an unusual form of transepithelial elimination of collagen and elastin fibres which are extruded through the epidermis in patients with a genetic predisposition or underlying diseases, such as diabetes mellitus or renal diseases. We present the unusual case of an 87-year-old diabetic male with a giant form of reactive perforating collagenosis and review the available literature.

Obesity, Sex, Race, and Early Onset Hypertension: Implications for a Refined Investigation Strategy.

Investigation for secondary causes is recommended in early onset hypertension. However, obesity is associated with higher blood pressure (BP), so investigation for alternative secondary causes may not be necessary in all obese patients. We sought to define a rational approach to investigation across strata of age, body mass index (BMI) sex and race, based on BP distributions in the US National Health and Nutrition Examination Surveys 2005 to 2016.

Sequential Treatment of Superficial Basal Cell Carcinomas With Topical Methyl Aminolevulinate Photodynamic Therapy and Imiquimod 5% Cream: A Retrospective Study of Clinical and Cosmetic Outcomes.

Background: Topical photodynamic therapy (PDT) and imiquimod 5% (IMQ) cream are established treatments for superficial basal cell carcinoma (sBCC). Both have high initial response rates and recurrence rates of up to 37%. Recent studies demonstrate that PDT and imiquimod may act on sBCCs via synergistic immunomodulatory pathways.

The color of skin: yellow diseases of the skin, nails, and mucosa.

The colors reflected from the skin are important indicators of dermatologic and systemic disorders. Incident light is subject to absorption by chromophores in the skin and scattering. Chromophores associated with yellow light reflection include the carotenoids and bilirubin.

Combination Therapy of Ipilimumab and Nivolumab-associated Toxic Epidermal Necrolysis (TEN) in a Patient With Metastatic Melanoma: A Case Report and Literature Review.

Ipilimumab and nivolumab are immune checkpoint inhibitors used in the treatment of metastatic melanoma. The authors report the case of a 62-year-old white male individual with metastatic choroidal melanoma who had commenced adjuvant systemic treatment with combination checkpoint inhibitor therapy of intravenous ipilimumab (anti-cytotoxic T-lymphocyte antigen-4) and nivolumab (anti-programmed cell death-1) at 3-week cycle intervals. On day 4 after the second cycle, he developed an acute widespread rash.

Changing Protein Permeability with Nephron Loss: Evidence for a Human Remnant Nephron Effect.

Background: If loss of functioning nephrons predisposes to glomerular barotrauma (a "remnant nephron" effect), then glomerular permeability should increase as glomerular filtration rate (GFR) falls, as is observed in animal models of nephron loss.

Methods: Changes in net renal protein permeability, defined as proteinuria or albuminuria per mL/min of GFR, were measured in the setting of nephron loss due to kidney donation (Assessing Long Term Outcomes in Living Kidney Donors cohort) or progressive chronic kidney disease (CKD; Modification of Diet in Renal Disease [MDRD], African American Study of Kidney Disease [AASK], and Chronic Renal insufficiency Cohort [CRIC] studies).

Results: Following kidney donation, renal albumin permeability increased by 31% from predonation levels (p < 0.

The methyltransferase SET9 regulates TGFB1 activation of renal fibroblasts via interaction with SMAD3.

Chronic kidney disease (CKD) is a global socioeconomic problem. It is characterised by the presence of differentiated myofibroblasts, which cause tissue fibrosis in response to TGFB1, leading to renal failure. Here, we define a novel interaction between the SET9 lysine methyltransferase (also known as SETD7) and SMAD3, the principal mediator of TGFB1 signalling in myofibroblasts.

Pseudogenization of the gene is common in the mitochondrial DNA of many vertebrates.

In the human the peptide Humanin is produced from the small gene which is embedded as a gene-within-a-gene in the 16S ribosomal molecule of the mitochondrial DNA (mtDNA). The peptide itself appears to be significant in the prevention of cell death in many tissues and improve cognition in animal models. By using simple data mining techniques, it is possible to show that 99.

Leber Hereditary Optic Neuropathy: A Mitochondrial Disease Unique in Many Ways.

Leber hereditary optic neuropathy (LHON) was the first mitochondrial disease to be identified as being caused by mutations in the mitochondrial DNA (mtDNA). This disease has been studied extensively in the past two decades, particularly in Brazilian, Chinese and European populations; and many primary mutations have been reported. However, the disease is enigmatic with many unique features, and there still are several important questions to be resolved.

Nutlin-3 inhibits androgen receptor-driven c-FLIP expression, resulting in apoptosis of prostate cancer cells.

Inhibition of androgen receptor (AR) signalling represents the conventional medical management of prostate cancer. Ultimately this treatment fails because tumors develop an incurable, castrate resistant phenotype, resulting in an unmet need for new treatments in prostate cancer. The AR remains a viable therapeutic target in castrate resistant disease, such that novel ways of downregulating AR activities are attractive as potential treatments.

Deep Retraction Pockets, Endometriosis, and Quality of Life.

Objective: The purpose of this study was to examine if deep retraction pockets (DRPs) in the posterior cul-de-sac and uterosacral ligaments could be a manifestation of endometriosis and if excision of these pockets improves pain symptoms and quality of life.

Study Design: Prospective cohort study Canadian Task Force Classification, II-3.

Materials And Methods: Preoperative data, operative data, and follow-up data were collected prospectively at the Center for Endometriosis at Saint Louis University, a referral center for the surgical management of endometriosis.

ZIKA--How fast does this virus mutate?

The World Health Organization has declared the present Zika virus epidemic to be a 'Public Health Emergency of International Concern'. The virus appears to have spread from Thailand to French Polynesia in 2013, and has since infected over a million people in the countries of South and Central America. In most cases the infection is mild and transient, but the virus does appear to be strongly neurotropic and the presumptive cause of both birth defects in fetuses and Guillain-Barré syndrome in some adults.

Mitochondrial DNA Haplogroup A Decreases the Risk of Drug Addiction but Conversely Increases the Risk of HIV-1 Infection in Chinese Addicts.

Drug addiction is one of the most serious social problems in the world today and addicts are always at a high risk of acquiring HIV infection. Mitochondrial impairment has been reported in both drug addicts and in HIV patients undergoing treatment. In this study, we aimed to investigate whether mitochondrial DNA (mtDNA) haplogroup could affect the risk of drug addiction and HIV-1 infection in Chinese.

The saga of the many studies wrongly associating mitochondrial DNA with breast cancer.

Background: A large body of genetic research has focused on the potential role that mitochondrial DNA (mtDNA) variants might play on the predisposition to common and complex (multi-factorial) diseases. It has been argued however that many of these studies could be inconclusive due to artifacts related to genotyping errors or inadequate design.

Methods: Analyses of the data published in case-control breast cancer association studies have been performed using a phylogenetic-based approach.

Indicators of pulmonary exacerbation in cystic fibrosis: A Delphi survey of patients and health professionals.

Background: There is uncertainty about the most important indicators of pulmonary exacerbations in CF.

Methods: Two parallel Delphi surveys in 13 CF centres (UK and Ireland). Delphi 1: 31 adults with CF, ≥ one exacerbation over 12 months.

The case for the continuing use of the revised Cambridge Reference Sequence (rCRS) and the standardization of notation in human mitochondrial DNA studies.

Since the determination in 1981 of the sequence of the human mitochondrial DNA (mtDNA) genome, the Cambridge Reference Sequence (CRS), has been used as the reference sequence to annotate mtDNA in molecular anthropology, forensic science and medical genetics. The CRS was eventually upgraded to the revised version (rCRS) in 1999. This reference sequence is a convenient device for recording mtDNA variation, although it has often been misunderstood as a wild-type (WT) or consensus sequence by medical geneticists.

Deubiquitinating enzyme Usp12 is a novel co-activator of the androgen receptor.

The androgen receptor (AR), a member of the nuclear receptor family, is a transcription factor involved in prostate cell growth, homeostasis, and transformation. AR is a key protein in growth and development of both normal and malignant prostate, making it a common therapeutic target in prostate cancer. AR is regulated by an interplay of multiple post-translational modifications including ubiquitination.