Vaccinia virus binds to the scavenger receptor MARCO on the surface of keratinocytes.

Patients with altered skin immunity, such as individuals with atopic dermatitis (AD), can have a life-threatening disruption of the epidermis known as eczema vaccinatum after vaccinia virus (VV) infection of the skin. Here, we sought to better understand the mechanism(s) by which VV associates with keratinocytes. The class A scavenger receptor known as MARCO (macrophage receptor with collagenous structure) is expressed on human and mouse keratinocytes and found to be abundantly expressed in the skin of patients with AD. VV bound directly to MARCO, and overexpression of MARCO increased susceptibility to VV infection. Furthermore, ligands with affinity for MARCO, or excess soluble MARCO, competitively inhibited VV infection. These findings indicate that MARCO promotes VV infection and highlights potential new therapeutic strategies for prevention of VV infection in the skin

On Some Generalizations Bellman-Bihari Result for Integro-Functional Inequalities for Discontinuous Functions and Their Applications

We present some new nonlinear integral inequalities Bellman-Bihari type with delay for discontinuous functions (integro-sum inequalities; impulse integral inequalities). Some applications of the results are included: conditions of boundedness (uniformly), stability by Lyapunov (uniformly), practical stability by Chetaev (uniformly) for the solutions of impulsive differential and integro-differential systems of ordinary differential equations

Teaching medical statistics to undergraduate medical students: what is taught and what is really useful for a medical professional? A report of the Education Committee of the Italian Society of Medical Statistics and Clinical Epidemiology (SISMEC)

Background: There is a large heterogeneity among the courses of medical statistics in Italian Medical Schools.  Aims: (1) To describe issues that are dealt with in the statistics undergraduate medical courses in Italian medical Schools. (2) To investigate which methodological topics are deemed as more useful for the education of undergraduate medical students by clinical teachers.  Methods: (1) An online questionnaire, covering the qualifying teaching issues of medical statistics, was sent to all academic biostatisticians, asking what they were teaching to undergraduate medical students. The reference year was 2015-2016. Undergraduate medical courses were the statistical units. (2) A second survey involved teachers of other medical disciplines with institutional roles, asking to score the usefulness for medical education of a number of topics concerning medical statistics, on a 5-point Likert scale. Only descriptive analyses were performed.  Results: Fifty-two (96%) case report forms (CRF) were returned from teachers of medical statistics. Most statistical and epidemiological topics were taught except comparison of >2 groups, impact of biases and standardization of rates. Conversely, issues of clinical epidemiology were neglected in about half of degree courses.  Thirty-three (31%) CRFs were returned from clinical teachers. The percentage of issues deemed very useful or essential ranged from 57% to 94%, with higher scores for those referring to critical assessment of the literature.  Conclusions: More extensive coverage of clinical epidemiology issues is needed to meet the demand of physicians, as responsible consumers of quantitative research. As biostatisticians we should operate to increase the homogeneity of medical statistics teaching in medical undergraduates’ educatio

Metastability of the three-state Potts model with general interactions

We consider the Potts model on a two-dimensional periodic rectangular lattice with general coupling constants $J_{ij}>0$, where $i,j\in\{1,2,3\}$ are the possible spin values (or colors). The resulting energy landscape is thus significantly more complex than in the original Ising or Potts models. The system evolves according to a Glauber-type spin-flipping dynamics. We focus on a region of the parameter space where there are two symmetric metastable states and a stable state, and the height of a direct path between the metastable states is equal to the height of a direct path between any metastable state and the stable state. We study the metastable transition time in probability and in expectation, the mixing time of the dynamics and the spectral gap of the system when the inverse temperature $\beta$ tends to infinity. Then, we identify all the critical configurations that are visited with high probability during the metastable transition.Comment: 35 pages, 8 figure

Criteria for standardising counselling for HIV testing

In the present work, we outline basic health counselling skills, specifically, those for performing pre-test and post-test counselling for HIV infection. The ultimate goal is to propose that counselling be performed in facilities that carry out screening for anti-HIV antibodies, following standardised (and thus replicable) criteria, with consistent focus on the quality of the relationship between the healthcare professional and the individual undergoing testing and on the individual's specific needs

The Streptomyces coelicolor small ORF trpM stimulates growth and morphological development and exerts opposite effects on actinorhodin and calcium-dependent antibiotic production

In actinomycetes, antibiotic production is often associated with a morpho-physiological differentiation program that is regulated by complex molecular and metabolic networks. Many aspects of these regulatory circuits have been already elucidated and many others still deserve further investigations. In this regard, the possible role of many small open reading frames (smORFs) in actinomycete morpho-physiological differentiation is still elusive. In Streptomyces coelicolor, inactivation of the smORF trpM (SCO2038) – whose product modulates L-tryptophan biosynthesis – impairs production of antibiotics and morphological differentiation. Indeed, it was demonstrated that TrpM is able to interact with PepA (SCO2179), a putative cytosol aminopeptidase playing a key role in antibiotic production and sporulation. In this work, a S. coelicolor trpM knock-in (Sco-trpMKI) mutant strain was generated by cloning trpM into overexpressing vector to further investigate the role of trpM in actinomycete growth and morpho-physiological differentiation. Results highlighted that trpM: (i) stimulates growth and actinorhodin (ACT) production; (ii) decreases calcium-dependent antibiotic (CDA) production; (iii) has no effect on undecylprodigiosin production. Metabolic pathways influenced by trpM knock- in were investigated by combining two-difference in gel electrophoresis/nanoliquid chromatography coupled to electrospray linear ion trap tandem mass spectrometry (2D- DIGE/nanoLC-ESI-LIT-MS/MS) and by LC-ESI-MS/MS procedures, respectively. These analyses demonstrated that over-expression of trpM causes an over-representation of factors involved in protein synthesis and nucleotide metabolism as well as a down-representation of proteins involved in central carbon and amino acid metabolism. At the metabolic level, this corresponded to a differential accumulation pattern of different amino acids – including aromatic ones but tryptophan – and central carbon intermediates. PepA was also down-represented in Sco-trpMKI. The latter was produced as recombinant His-tagged protein and was originally proven having the predicted aminopeptidase activity. Altogether, these results highlight the stimulatory effect of trpM in S. coelicolor growth and ACT biosynthesis, which are elicited through the modulation of various metabolic pathways and PepA representation, further confirming the complexity of regulatory networks that control antibiotic production in actinomycetes

Critical configurations and tube of typical trajectories for the Potts and Ising models with zero external field

We consider the ferromagnetic q-state Potts model with zero external field in a finite volume evolving according to Glauber-type dynamics described by the Metropolis algorithm in the low temperature asymptotic limit. Our analysis concerns the multi-spin system that has q stable equilibria. Focusing on grid graphs with periodic boundary conditions, we study the tunneling between two stable states and from one stable state to the set of all other stable states. In both cases we identify the set of gates for the transition and prove that this set has to be crossed with high probability during the transition. Moreover, we identify the tube of typical paths and prove that the probability to deviate from it during the transition is exponentially small.Comment: 44 pages, 15 figures. All comments are welcome