F1000Prime Reports

In-group favoritism is the tendency for individuals to cooperate with in-group members more strongly than with out-group members. Similar concepts have been described across different domains, including in-group bias, tag-based cooperation, parochial altruism, and ethnocentrism. Both humans and other animals show this behavior. Here, we review evolutionary mechanisms for explaining this phenomenon by covering recently developed mathematical models. In fact, in-group favoritism is not easily realized on its own in theory, although it can evolve under some conditions...

In development and disease, vascular endothelial growth factor (VEGF) regulates the expansion of the vascular tree. In response to hypoxia, VEGF promotes new capillary formation through the process of angiogenesis by inducing endothelial cell sprouting, proliferation, and migration. Wound healing, tissue regeneration, and tumor growth depend on angiogenesis for adequate nutrient and oxygen delivery. Under different conditions, VEGF promotes arterial growth, modulates lumen expansion, and induces collateral vessel formation, events collectively referred to as arteriogenesis...

Plasmodesmata (PDs) are microscopic channels that connect virtually every plant cell to its neighbors. They also provide a route for molecules to access the phloem for systemic movement throughout the plant. In this report, I review recent findings that broaden the potential impact of these channels, by revealing their contribution to auxin movement and as potential sites of receptor signaling. These discoveries should prompt a reassessment of symplasmic connectivity and its importance to plant development, defense, and physiology...

Pre-eclampsia complicates around 5% of pregnancies and hypertensive disorders of pregnancy are responsible for over 60,000 maternal deaths worldwide annually. Pre-eclampsia is characterized by hypertension and features of multiple organ disease. Diagnosis remains a challenge as clinical presentation is highly variable and even with severe disease a woman can be asymptomatic. Pre-eclampsia is characterized by abnormal placentation with subsequent maternal inflammatory and vascular response. Improved understanding of the underlying pathophysiology relating to the role of angiogenic factors, has emerged and placed intense interest on their role in prognostic modelling or diagnosis of pre-eclampsia...

Over the last few decades, our understanding of directed cell growth in different organisms has substantially improved. Tip-growing cells in plants elongate rapidly via targeted deposition of cell wall and membrane material at the cell apex, and use turgor pressure as a driving force for expansion. This type of polar growth requires a high degree of coordination between a plethora of cellular and extracellular components and compounds, including calcium dynamics, apoplastic reactive oxygen species and pH, the cytoskeleton, and vesicular trafficking...

Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration at suppressive doses, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of (131)I in their metastases. Two thirds of distant metastases will become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits...

The potential of the systemic antifungal treatment of non-immunocompromised patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown, although it represents three out of four antifungal treatments prescribed in intensive care units. It may allow an early treatment of invasive fungal infection at incubation phase, but exposes patients to unnecessary antifungal treatments with subsequent costs and antifungal selection pressure. As early diagnostic tests for invasive candidiasis are still considered insufficient, the potential of this strategy needs to be demonstrated by a randomized controlled trial...

Permanent primary congenital hypothyroidism (CH), the commonest cause of preventable intellectual disability, is due to defects in the embryonic development of the thyroid in the vast majority of cases. These defects are collectively called thyroid dysgenesis. The thyroid may be absent (athyreosis) but, more commonly, a sublingual thyroid ectopy without lateral lobes, is the only thyroid tissue present. Such an ectopy presumably results from an arrest in the downward migration of the median anlage. Thyroid ectopy almost always occurs in a sporadic fashion...

Plants use auxin to relay critical information that shapes their growth and development. Auxin perception and transcriptional activation are mediated by the degradation of Aux/IAA repressor proteins. Degradation of Aux/IAAs relieves repression on Auxin Response Factors (ARFs), which bind DNA sequences called Auxin Response Elements (AuxREs). In most higher plant genomes, multiple paralogs exist for each part of the auxin nuclear signaling pathway. This potential combinatorial diversity in signaling pathways likely contributes to the myriad of context-specific responses to auxin...

Autophagy is a catabolic degradation process in which cellular proteins and organelles are engulfed by double-membrane autophagosomes and degraded in lysosomes. Autophagy has emerged as a critical pathway in tumor development and cancer therapy, although its precise function remains a conundrum. The current consensus is that autophagy has a dual role in cancer. On the one hand, autophagy functions as a tumor suppressor mechanism by preventing the accumulation of damaged organelles and aggregated proteins. On the other hand, autophagy is a key cell survival mechanism for established tumors; therefore autophagy inhibition suppresses tumor progression...

Despite recent advances in delineating the pathogenic mechanisms of autoimmune disease, the puzzle that reveals the true picture of these diverse immunological disorders is yet to be solved. We know that the human leukocyte antigen (HLA) loci as well as many different genetic susceptibility loci with relatively small effect sizes predispose to various autoimmune diseases and that environmental factors are involved in triggering disease. Models for mechanisms of disease become increasingly complex as relationships between components of both the adaptive and innate immune systems are untangled at the molecular level...

Inhaled glucocorticoids acting via the glucocorticoid receptor are a mainstay treatment option for individuals with asthma. There is a consensus that the remedial actions of inhaled glucocorticoids are due to their ability to suppress inflammation by modulating gene expression. While inhaled glucocorticoids are generally effective in asthma, there are subjects with moderate-to-severe disease in whom inhaled glucocorticoids fail to provide adequate control. For these individuals, asthma guidelines recommend that a long-acting β2-adrenoceptor agonist (LABA) be administered concurrently with an inhaled glucocorticoid...

Inflammation is a double-edged sword. While short-lived, acute inflammation is essential for the repair and resolution of infection and damage, uncontrolled and unresolved chronic inflammation is central to several diseases, including cancer, autoimmune diseases, allergy, metabolic disease, and cardiovascular disease. This report aims to review the literature regarding several members of the nucleotide-binding domain, leucine-rich repeat-containing receptor (NLR) family of pattern recognition sensors/receptors that serve as checkpoints for inflammation...

All living organisms depend on primary and secondary membrane transport for the supply of external nutrients and removal or sequestration of unwanted (toxic) compounds. Due to the chemical diversity of cellular molecules, it comes as no surprise that a significant part of the proteome is dedicated to the active transport of cargo across the plasma membrane or the membranes of subcellular organelles. Transport against a chemical gradient can be driven by, for example, the free energy change associated with ATP hydrolysis (primary transport), or facilitated by the potential energy of the chemical gradient of another molecule (secondary transport)...

The phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling network is a master regulator of processes that contribute to tumorigenesis and tumor maintenance. The PI3K pathway also plays a critical role in driving resistance to diverse anti-cancer therapies. This review article focuses on mechanisms by which the PI3K pathway contributes to therapy resistance in cancer, and highlights potential combination therapy strategies to circumvent resistance driven by PI3K signaling. In addition, resistance mechanisms that limit the clinical efficacy of small molecule inhibitors of the PI3K pathway are discussed...

Our current understanding of glucose homeostasis is centered on glucose-induced secretion of insulin from pancreatic islets and insulin action on glucose metabolism in peripheral tissues. In addition, however, recent evidence suggests that neurocircuits located within a brain-centered glucoregulatory system work cooperatively with pancreatic islets to promote glucose homeostasis. Among key observations is evidence that, in addition to insulin-dependent mechanisms, the brain has the capacity to potently lower blood glucose levels via mechanisms that are insulin-independent, some of which are activated by signals emanating from the gastrointestinal tract...

Whether or not Borrelia burgdorferi can persist after conventional treatment with antimicrobials has been a very controversial issue. Two recent studies took different approaches to try to answer this question. In one, investigators showed that, in each of 22 instances in 17 patients with two consecutive episodes of culture-proved erythema migrans, the strains of B. burgdorferi were different based on their genotypes. This indicated that the repeat episodes were due to new infections rather than recrudescence of the original infection...

Implantable cardioverter-defibrillators are complex technical devices with a multitude of programming options for the physician. In recent years, numerous randomized trials have been performed to define the optimal programming strategies and have provided valuable insights, especially in primary prevention patients. This article provides an actual overview on the existing evidence on the most important programming features for accurate detection and therapy of ventricular arrhythmias.

Mast cells are immune cells that accumulate in the tumors and their microenvironment during disease progression. Mast cells are armed with a wide array of receptors that sense environment modifications and, upon stimulation, they are able to secrete several biologically active factors involved in the modulation of tumor growth. For example, mast cells are able to secrete pro-angiogenic and growth factors but also pro- and anti-inflammatory mediators. Recent studies have allowed substantial progress in understanding the role of mast cells in tumorigenesis/disease progression but further studies are necessary to completely elucidate their impact in the pathophysiology of cancer...

Acute myocardial infarction (AMI) and sudden cardiac death (SCD) are among the most serious and catastrophic of acute cardiac disorders, accounting for hundreds of thousands of deaths each year worldwide. Although the incidence of AMI has been decreasing in the US according to the American Heart Association, heart disease is still the leading cause of mortality in adults. In most cases of AMI and in a majority of cases of SCD, the underlying pathology is acute intraluminal coronary thrombus formation within an epicardial coronary artery leading to total or near-total acute coronary occlusion...