Quantitative comparison of presenilin protein expression reveals greater activity of PS2-γ-secretase.

γ-secretase processing of amyloid precursor protein (APP) has long been of interest in the pathological progression of Alzheimer's disease (AD) due to its role in the generation of amyloid-β. The catalytic component of the enzyme is the presenilins of which there are two homologues, Presenilin-1 (PS1) and Presenilin-2 (PS2). The field has focussed on the PS1 form of this enzyme, as it is typically considered the more active at APP processing.

Winner-loser effects improve social network efficiency between competitors with equal resource holding power.

Animal societies are structured of dominance hierarchy (DH). DH can be viewed as networks and analyzed by graph theory. We study the impact of state-dependent feedback (winner-loser effect) on the emergence of local dominance structures after pairwise contests between initially equal-ranking members (equal resource-holding-power, RHP) of small and large social groups.

Significant, but not biologically relevant: Nosema ceranae infections and winter losses of honey bee colonies.

The Western honey bee Apis mellifera, which provides about 90% of commercial pollination, is under threat from diverse abiotic and biotic factors. The ectoparasitic mite Varroa destructor vectoring deformed wing virus (DWV) has been identified as the main biotic contributor to honey bee colony losses worldwide, while the role of the microsporidium Nosema ceranae is still controversially discussed. In an attempt to solve this controversy, we statistically analyzed a unique data set on honey bee colony health collected from a cohort of honey bee colonies over 15 years and comprising more than 3000 data sets on mite infestation levels, Nosema spp.

PRI: Re-Analysis of a Public Mass Cytometry Dataset Reveals Patterns of Effective Tumor Treatments.

Recently, mass cytometry has enabled quantification of up to 50 parameters for millions of cells per sample. It remains a challenge to analyze such high-dimensional data to exploit the richness of the inherent information, even though many valuable new analysis tools have already been developed. We propose a novel algorithm "pattern recognition of immune cells (PRI)" to tackle these high-dimensional protein combinations in the data.

X-Linked Agammaglobulinemia: Infection Frequency and Infection-Related Mortality in the USIDNET Registry.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to B lymphocyte deficiency and susceptibility to infection. A potential benefit of earlier diagnosis and treatment initiation on morbidity and mortality in XLA is incompletely understood. In the USIDNET Registry, we describe infection frequency and infection-related mortality in patients with XLA and their relationship to age of diagnosis and treatment initiation.

Evaluation of Virtual Screening Strategies for the Identification of γ-Secretase Inhibitors and Modulators.

γ-Secretase is an intramembrane aspartyl protease that is important in regulating normal cell physiology via cleavage of over 100 transmembrane proteins, including Amyloid Precursor Protein (APP) and Notch family receptors. However, aberrant proteolysis of substrates has implications in the progression of disease pathologies, including Alzheimer's disease (AD), cancers, and skin disorders. While several γ-secretase inhibitors have been identified, there has been toxicity observed in clinical trials associated with non-selective enzyme inhibition.

Skin Substitute Preparation Method Induces Immunomodulatory Changes in Co-Incubated Cells through Collagen Modification.

Chronic ulcerative and hard-healing wounds are a growing global concern. Skin substitutes, including acellular dermal matrices (ADMs), have shown beneficial effects in healing processes. Presently, the vast majority of currently available ADMs are processed from xenobiotic or cadaveric skin.

Abdominoplasty Skin-Based Dressing for Deep Wound Treatment-Evaluation of Different Methods of Preparation on Therapeutic Potential.

The management of hard-to-heal wounds is a significant clinical challenge. Acellular dermal matrices (ADMs) have been successfully introduced to enhance the healing process. Here, we aimed to develop protocol for the preparation of novel ADMs from abdominoplasty skin.

Differential Response of MDA-MB-231 and MCF-7 Breast Cancer Cells to In Vitro Inhibition with CTLA-4 and PD-1 through Cancer-Immune Cells Modified Interactions.

Drugs targeting immune checkpoint molecules have been found effective in melanoma, lung cancer, and other malignancies treatment. Recent studies on breast cancer demonstrated the significance of inhibitory anti-CTLA-4 and anti-PD-1 in the regulation of disease progression. However, seemingly the same types of breast cancer do not always respond unambiguously to immunotherapy.

Chronic stress and Alzheimer's disease: the interplay between the hypothalamic-pituitary-adrenal axis, genetics and microglia.

Chronic psychosocial stress is increasingly being recognised as a risk factor for sporadic Alzheimer's disease (AD). The hypothalamic-pituitary-adrenal axis (HPA axis) is the major stress response pathway in the body and tightly regulates the production of cortisol, a glucocorticoid hormone. Dysregulation of the HPA axis and increased levels of cortisol are commonly found in AD patients and make a major contribution to the disease process.

Identification and mapping of a novel resistance gene to the rice pathogen, Cercospora janseana.

The genetic architecture of resistance to Cercospora janseana was examined, and a single resistance locus was identified. A SNP marker was identified and validated for utilization in U.S.

Is Associated with Amyloid-β and ε4-Related Cognitive Decline in Cognitively Normal Adults.

Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease.

Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults.

Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study.

Relevance of a Truncated PRESENILIN 2 Transcript to Alzheimer's Disease and Neurodegeneration.

Background: The PRESENILIN genes (PSEN1, PSEN2) encoding for their respective proteins have critical roles in many aspects of Alzheimer's disease (AD) pathogenesis. The PS2V transcript of PSEN2 encodes a truncated protein and is upregulated in AD brains; however, its relevance to AD and disease progression remains to be determined.

Objective: Assess transcript levels in postmortem AD and non-AD brain tissue and in lymphocytes collected under the Australian Imaging Biomarker and Lifestyle (AIBL) study.

Chain Reversion for Detecting Associations in Interacting Variables-St. Nicolas House Analysis.

(1) Background: We present a new statistical approach labeled as "St. Nicolas House Analysis" (SNHA) for detecting and visualizing extensive interactions among variables. (2) Method: We rank absolute bivariate correlation coefficients in descending order according to magnitude and create hierarchic "association chains" defined by sequences where reversing start and end point does not alter the ordering of elements.

The influence of patient's age on metabolic and bariatric results of laparoscopic sleeve gastrectomy in 2-year observation.

Background: The incidence of obesity has been constantly growing and bariatric procedures are considered to be the most effective treatment solution for morbidly obese patients. The results of laparoscopic sleeve gastrectomy (LSG) may differ depending on patient's age, gender, preoperative body mass index (BMI) and physical activity.

Methods: The aim of this study was to evaluate age-related differences in the outcome of LSG in terms of weight loss parameters, lipid and carbohydrate profile.

Traumatized women's infants are bigger than children of mothers without traumas.

Life history theory predicts that experiencing stress during the early period of life will result in accelerated growth and earlier maturation. Indeed, animal and some human studies documented a faster pace of growth in the offspring of stressed mothers. Recent advances in epigenetics suggest that the effects of early developmental stress might be passed across the generations.

Ovine congenital progressive muscular dystrophy (OCPMD) is a model of TNNT1 congenital myopathy.

Ovine congenital progressive muscular dystrophy (OCPMD) was first described in Merino sheep flocks in Queensland and Western Australia in the 1960s and 1970s. The most prominent feature of the disease is a distinctive gait with stiffness of the hind limbs that can be seen as early as 3 weeks after birth. The disease is progressive.

The end of the secular trend in Norway: spatial trends in body height of Norwegian conscripts in the 19, 20 and 21 century.

We aimed to examine the distribution and secular changes of conscript body height in the geographic network of Norway since 1878 and to study its association with the degree of urbanization, and population density. Data on body height of Norwegian military conscripts were provided by the Statistics Norway Department (SSB). The sample comprised eight cohorts with the following measurement years: 1 1877, 1878 and 1880, 2 1895-1897, 3 1915-1917, 4 1935-1937, 5 1955-1957, 6 1975-1977, 7 1995-1997, and 8 2009-2011.

Environmental stimulation on height: The story from Indonesia.

: Since the 19 century, sexual dimorphism has been known to be sensitive to adverse environmental conditions. Migrants are sensitive to economic and political affluence, and tend to adjust in height towards height of their hosts. We aim to study growth, sexual dimorphism, and height of native and migrant children in three primary schools in Nabire, Papua, Indonesia.

Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception.

Dysregulated cytokine expression by T cells plays a pivotal role in the pathogenesis of autoimmune diseases. However, the identification of the corresponding pathogenic subpopulations is a challenge, since a distinction between physiological variation and a new quality in the expression of protein markers requires combinatorial evaluation. Here, we were able to identify a super-functional follicular helper T cell (Tfh)-like subpopulation in lupus-prone NZBxW mice with our binning approach "pattern recognition of immune cells (PRI)".