Drosophila as a Model for Human Diseases-Focus on Innate Immunity in Barrier Epithelia.

Epithelial immunity protects the host from harmful microbial invaders but also controls the beneficial microbiota on epithelial surfaces. When this delicate balance between pathogen and symbiont is disturbed, clinical disease often occurs, such as in inflammatory bowel disease, cystic fibrosis, or atopic dermatitis, which all can be in part linked to impairment of barrier epithelia. Many innate immune receptors, signaling pathways, and effector molecules are evolutionarily conserved between human and Drosophila.

Assays for Identifying Inducers of the Antimicrobial Peptide LL-37.

One promising approach to meet the growing problem of antibiotic resistance is to modulate host defense mechanisms, i.e., host-directed therapy (HDT), in the fight against infections.

Genomic analysis reveals the presence of a class D beta-lactamase with broad substrate specificity in animal bite associated Capnocytophaga species.

Capnocytophga canimorsus and Capnocytophga cynodegmi can be transmitted from cats and dogs to humans, and can cause a wide range of infections including wound infections, sepsis, or endocarditis. We and others recently discovered two new Capnocytophaga species, C. canis and C.

Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort.

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously.

Potent Inducers of Endogenous Antimicrobial Peptides for Host Directed Therapy of Infections.

A new concept for treatment of infections is induction of our own antimicrobial peptides and the presented novel class of inducer, aroylated phenylenediamines (APDs), gives up to 20 to 30-fold induction of the human antimicrobial peptide LL-37, in vitro. In addition, oral administration of an APD in a rabbit model of Shigellosis resulted in recovery from the infection in a few days implying that APD's are promising candidates for treatment of infections.

Auditory-Induced Emotion Mediates Perceptual Categorization of Everyday Sounds.

Research has shown that emotion categorization plays an important role in perception and categorization in the visual domain. In the present paper, we investigated the role of auditory-induced emotions for auditory perception. We further investigated whether the emotional responses mediate other perceptual judgments of sounds.

BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness: Associations with Working Memory Function.

Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity by mediating changes in cortical thickness and synaptic density in response to physical activity and environmental enrichment. Previous studies suggest that physical exercise can augment BDNF levels, both in serum and the brain, but no other study has examined how different types of activities compare with physical exercise in their ability to affect BDNF levels. By using a balanced cross over experimental design, we exposed nineteen healthy older adults to 35-minute sessions of physical exercise, cognitive training, and mindfulness practice, and compared the resulting changes in mature BDNF levels between the three activities.

Phosphoglycerate Kinase-A Novel Streptococcal Factor Involved in Neutrophil Activation and Degranulation.

Background:  Neutrophils have been proposed as important contributors to the hyperinflammatory responses that are associated with severe invasive Streptococcus pyogenes infections. In particular, streptococcal surface proteins have been implicated as potent neutrophil activators. Here we explore the impact of streptococcus-secreted factors on neutrophil activation and degranulation.

Human lung natural killer cells are predominantly comprised of highly differentiated hypofunctional CD69CD56 cells.

Background: In contrast to the extensive knowledge about human natural killer (NK) cells in peripheral blood, relatively little is known about NK cells in the human lung. Knowledge about the composition, differentiation, and function of human lung NK cells is critical to better understand their role in diseases affecting the lung, including asthma, chronic obstructive pulmonary disease, infections, and cancer.

Objective: We sought to analyze and compare the phenotypic and functional characteristics of NK cells in the human lung and peripheral blood at the single-cell level.

Self-Reported Physical Quality of Life Before Thoracic Operations Is Associated With Long-Term Survival.

Background: The aim was to analyze the association between baseline self-reported health-related quality of life and long-term survival after thoracic operations.

Methods: In a prospective population-based cohort study, we included patients scheduled for thoracic operations and obtained information about preoperative health-related quality of life using the validated quality-of-life instrument Short Form-36. Patients were categorized according to higher or lower physical and mental component scores, compared with an age- and sex-matched reference population.

Vitamin D3 Supplementation and Antibiotic Consumption - Results from a Prospective, Observational Study at an Immune-Deficiency Unit in Sweden.

Background: Vitamin D supplementation has been proposed to improve clinical symptoms during respiratory tract infections (RTIs), but results from randomized, placebo-controlled trials (RCT) are inconclusive. Previously, we performed an RCT in patients with various immune-disorders and observed that supplementation with 4000 IU vitamin D/day during 12 months significantly reduced antibiotic consumption and RTIs. This formed the basis for new guidelines at our unit; i.

Entinostat up-regulates the CAMP gene encoding LL-37 via activation of STAT3 and HIF-1α transcription factors.

Bacterial resistance against classical antibiotics is a growing problem and the development of new antibiotics is limited. Thus, novel alternatives to antibiotics are warranted. Antimicrobial peptides (AMPs) are effector molecules of innate immunity that can be induced by several compounds, including vitamin D and phenyl-butyrate (PBA).

Antibiotic Treatment in End-of-Life Cancer Patients-A Retrospective Observational Study at a Palliative Care Center in Sweden.

Background: The aim of this study was to elucidate whether palliative cancer patients benefit from antibiotic treatment in the last two weeks of life when an infection is suspected.

Method: We reviewed medical records from 160 deceased palliative cancer patients that had been included in previous studies on vitamin D and infections. Patients treated with antibiotics during the last two weeks of life were identified and net effects of treatment (symptom relief) and possible adverse events were extracted from medical records.

A One Health overview, facilitating advances in comparative medicine and translational research.

A1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N.

Ephrin B3 interacts with multiple EphA receptors and drives migration and invasion in non-small cell lung cancer.

Ephrin receptors (Ephs) are reported to control metastatic signaling of non-small cell lung cancer (NSCLC) and other tumors. Here we show for the first time that blocking expression of the Eph ligand Ephrin B3 inhibits NSCLC cell migration and invasion. We demonstrate that Ephrin B3 directly binds the EphAs EphA2, EphA3, EphA4, and EphA5.

Perioperative Cefovecin to Reduce the Incidence of Urinary Tract Infection in Dogs Undergoing Hemilaminectomy.

The prevalence of urinary tract infections (UTIs) in dogs with Type I intervertebral disc extrusion has been reported as high as 38% within 6 wk of surgery. Proper treatment of a UTI is important with myelopathy because it is a risk factor for persistent infection and reinfection in dogs. The study authors' investigated the incidence of UTIs in dogs having received either cefovecin or cefazolin as a preoperative prophylactic antibiotic for thoracolumbar hemilaminectomy.

[Biochemical changes after strenuous exercise – data from the Kalmar Ironman].

Biochemical changes after strenuous exercise - data from the Kalmar Ironman Strenuous and prolonged exercise like marathon, ultra running and triathlon can lead to changes in biomarkers of cardiac, muscle and kidney functional damage. We present the data of 30 (15 men, 15 women) participants of the Kalmar Ironman 2015. Pre-race electrocardiograms and echocardiograms showed a high frequency of abnormalities.

Functional CRISPR screening identifies the ufmylation pathway as a regulator of SQSTM1/p62.

SQSTM1 is an adaptor protein that integrates multiple cellular signaling pathways and whose expression is tightly regulated at the transcriptional and post-translational level. Here, we describe a forward genetic screening paradigm exploiting CRISPR-mediated genome editing coupled to a cell selection step by FACS to identify regulators of SQSTM1. Through systematic comparison of pooled libraries, we show that CRISPR is superior to RNAi in identifying known SQSTM1 modulators.

Amyloid formation: functional friend or fearful foe?

Amyloid formation has been most studied in the context of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, as well as in amyloidosis. However, it is becoming increasingly clear that amyloid is also present in the healthy setting; for example nontoxic amyloid formation is important for melanin synthesis and in innate immunity. Furthermore, bacteria have mechanisms to produce functional amyloid structures with important roles in bacterial physiology and interaction with host cells.

Circulating miR-150 in CSF is a novel candidate biomarker for multiple sclerosis.

Objective: To explore circulating microRNAs (miRNAs) in cell-free CSF as novel biomarkers for multiple sclerosis (MS).

Methods: Profiling of miRNAs in CSF of pooled patients with clinically isolated syndrome (CIS), patients with relapsing-remitting MS, and inflammatory and noninflammatory neurologic disease controls was performed using TaqMan miRNA arrays. Two independent patient cohorts (n = 142 and n = 430) were used for validation with real-time PCR.

No Evidence for Disease History as a Risk Factor for Narcolepsy after A(H1N1)pdm09 Vaccination.

Objectives: To investigate disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy.

Methods: Case-control study in Sweden. Cases included persons referred for a Multiple Sleep Latency Test between 2009 and 2010, identified through diagnostic sleep centres and confirmed through independent review of medical charts.

Detection of Adult Green Sturgeon Using Environmental DNA Analysis.

Environmental DNA (eDNA) is an emerging sampling method that has been used successfully for detection of rare aquatic species. The Identification of sampling tools that are less stressful for target organisms has become increasingly important for rare and endangered species. A decline in abundance of the Southern Distinct Population Segment (DPS) of North American Green Sturgeon located in California's Central Valley has led to its listing as Threatened under the Federal Endangered Species Act in 2006.

Vitamin D and patients with palliative cancer.

Vitamin D is a hormone that is synthesised in the skin in the presence of sunlight. Sufficient vitamin D levels are important-not only for a healthy skeleton-but also for a healthy immune system. Many patients with cancer have insufficient vitamin D levels, and low vitamin D levels are associated with increased 'all-cause mortality' and especially mortality due to cancer.

Retrospective evaluation of toceranib phosphate (Palladia®) toxicity in cats.

The purpose of this study was to describe the toxicity profile of toceranib phosphate in tumour bearing cats. Medical records were reviewed from seven institutions. Patients with incomplete medical records and those receiving concurrent chemotherapy or NSAIDs (non-steroidal anti-inflammatory) were excluded.

Whole genome sequencing identifies a novel species of the genus Capnocytophaga isolated from dog and cat bite wounds in humans.

C. canimorsus and C. cynodegmi are dog and cat commensals which can be transmitted to humans via bites or scratches and can cause sepsis, meningitis, endocarditis, and eye- or wound infections.