Mammary Stem Cell Self-Renewal Is Regulated by Slit2/Robo1 Signaling through SNAI1 and mINSC.

Tissue homeostasis requires somatic stem cell maintenance; however, mechanisms regulating this process during organogenesis are not well understood. Here, we identify asymmetrically renewing basal and luminal stem cells in the mammary end bud. We demonstrate that SLIT2/ROBO1 signaling regulates the choice between self-renewing asymmetric cell divisions (ACDs) and expansive symmetric cell divisions (SCDs) by governing Inscuteable (mInsc), a key member of the spindle orientation machinery, through the transcription factor Snail (SNAI1). Loss of SLIT2/ROBO1 signaling increases SNAI1 in the nucleus. Overexpression of SNAI1 increases mInsc expression, an effect that is inhibited by SLIT2 treatment. Increased mInsc does not change cell proliferation in the mammary gland (MG) but instead causes more basal cap cells to divide via SCD, at the expense of ACD, leading to more stem cells and larger outgrowths. Together, our studies provide insight into how the number of mammary stem cells is regulated by the extracellular cue SLIT2.

Evolutionary screening and adsorption behavior of engineered M13 bacteriophage and derived dodecapeptide for selective decoration of gold interfaces.

There is a growing interest in identifying biomacromolecules such as proteins and peptides to functionalize metallic surfaces through noncovalent binding. One method for functionalizing materials without fundamentally changing their inherent structure is using biorecognition moieties. Here, we proved a general route to select a biomolecule adhesive motif for surface functionalization by comprehensively screening phage displayed peptides. In particular, we selected a genetically engineered M13 bacteriophage and a linear dodecapeptide derived from its pIII domain for recognizing gold surfaces in a specific and selective manner. In the phage context, we demonstrated the adhesive motif was capable to adsorb on gold in a preferential way with a morphological and viscoelastic signature of the adsorbed layer as evidenced by QCM-D and AFM investigations. Out of the phage context, the linear dodecapeptide is reproducibly found to adhere to the gold surface, and by quantitative SPR measurements, high affinity constants (K(eq)~10(6)M(-1), binding energy ~-8 kcal/mol) were determined. We proved that the interactions occurring at gold interface were mainly hydrophobic as a consequence of high frequency of hydrophobic residues in the peptide sequence. Moreover, by CD, molecular dynamics and steered molecular dynamics, we demonstrated that the molecular flexibility only played a minor role in the peptide adsorption. Such noncovalent but specific modification of inorganic surfaces through high affinity biomolecule adsorption represents a general strategy to modulate the functionality of multipurpose metallic surfaces.

A roundabout way to cancer.

The Slit family of secreted proteins and their transmembrane receptor, Robo, were originally identified in the nervous system where they function as axon guidance cues and branching factors during development. Since their discovery, a great number of additional roles have been attributed to Slit/Robo signaling, including regulating the critical processes of cell proliferation and cell motility in a variety of cell and tissue types. These processes are often deregulated during cancer progression, allowing tumor cells to bypass safeguarding mechanisms in the cell and the environment in order to grow and escape to new tissues. In the past decade, it has been shown that the expression of Slit and Robo is altered in a wide variety of cancer types, identifying them as potential therapeutic targets. Further, studies have demonstrated dual roles for Slits and Robos in cancer, acting as both oncogenes and tumor suppressors. This bifunctionality is also observed in their roles as axon guidance cues in the developing nervous system, where they both attract and repel neuronal migration. The fact that this signaling axis can have opposite functions depending on the cellular circumstance make its actions challenging to define. Here, we summarize our current understanding of the dual roles that Slit/Robo signaling play in development, epithelial tumor progression, and tumor angiogenesis.

First-episode psychosis at the West Bologna Community Mental Health Centre: results of an 8-year prospective study.

BACKGROUND: Research mostly conducted in the UK and northern Europe has established that there are high rates of first-episode psychosis (FEP) in large cities and immigrant populations; moreover, psychosis has been found to be associated with cannabis use and early trauma. The present study aimed to evaluate the incidence rate of FEP and the distribution of several risk factors (e.g. age, ethnicity, substance abuse) in Bologna, Italy. METHOD: The Bologna FEP (BoFEP) study is an 8-year prospective study. All FEP patients, 18-64 years old, consecutively referred to the West Bologna Community Mental Health Centre (CMHC) from 2002 to 2009 were evaluated. Sociodemographic information, migration history and clinical data were collected through an ad-hoc schedule. Psychiatric diagnoses were recorded using the Schedule for Clinical Assessment of Neuropsychiatry (SCAN). RESULTS: The overall incidence rate (IR) in the BoFEP study was 16.4 per 100 000 person-years [95% confidence interval (CI) 13.9-18.9]. The incidence was higher in young people, men and migrants (MI). CONCLUSIONS: The IR of FEP found by the Bologna study is lower than that found by other European studies. However, as in other studies, the incidence was higher in certain groups. This heterogeneity has implications for policy and mental health service development, and for understanding the aetiology of psychosis.

Determinants of surgical delay for hip fracture.

BACKGROUND AND OBJECTIVE: Recent guidelines recommend early surgical treatment of hip fractures in the elderly. The aim of the present study is to analyse the factors delaying surgical treatment of hip fractures in elderly patients by more than 2 days and to investigate whether these factors are consistent between a teaching and a community hospital. DESIGN: Retrospective cohort study using hospital discharge records and patients' charts. SETTING: Orthopaedics and traumatology departments of a teaching hospital and a small town hospital in Northern Italy. PARTICIPANTS: 1768 consecutive patients aged 65 years or more who underwent surgery for hip fractures between 2004 and 2007. INTERVENTIONS: Surgery for hip fracture. MAIN OUTCOME MEASURE(S): Surgery within two days from admission. RESULTS: 938 (53.1%) patients were operated within 2 days of admission to the hospital. Logistic regression models were used to examine potential predictors of surgery delay including gender, age, hospital, comorbidity, type of intervention (partial or total hip replacement, reduction and internal fixation), International Normalized Ratio (INR), Haemoglobin (Hb), American Society of Anaesthesiologists (ASA) score, and day of admission (categorized as Monday to Wednesday, Thursday-Friday, Saturday-Sunday). Age, type of intervention (partial or total hip replacement), INR score > 1.5 and an ASA score of 4 compared to 1-2, admission on Thursday-Friday or Saturday-Sunday and the interaction hospital × arrhythmia significantly predicted a surgery delay of more than 2 days. CONCLUSIONS: Both organization and medical problems accounted for delays of surgical treatment of hip fractures. Established protocols aimed to optimize the patient flow logistics and to manage comorbidities are crucial to make hospitals more patient-centred and to improve patient outcomes.