Pseudomonas aeruginosa is an opportunistic pathogen that is frequently associated with both acute and chronic infections. P. aeruginosa possesses a complex regulatory network that modulates nutrient acquisition and virulence, but our knowledge of these networks is largely based on studies with shaking cultures, which are not likely representative of conditions during infection. Here, we provide proteomic, metabolic, and genetic evidence that regulation by iron, a critical metallonutrient, is altered in static P. aeruginosa cultures. Specifically, we observed a loss of iron-induced expression of proteins for oxidative phosphorylation, tricarboxylic acid (TCA) cycle metabolism under static conditions. Moreover, we identified type VI secretion as a target of iron regulation in P. aeruginosa cells under static but not shaking conditions, and we present evidence that this regulation occurs via PrrF small regulatory RNA (sRNA)-dependent production of 2-alkyl-4(1H)-quinolone metabolites. These results yield new ironzation of distinct growth models can enhance our understanding of basic physiological processes that may also affect pathogenesis.Cyclic di-AMP (c-di-AMP) is an essential and ubiquitous second messenger among bacteria. c-di-AMP regulates many cellular pathways through direct binding to several molecular targets in bacterial cells. c-di-AMP depletion is well known to destabilize the bacterial cell wall, resulting in increased bacteriolysis and enhanced susceptibility to cell wall targeting antibiotics. Using the human pathogen Listeria monocytogenes as a model, we found that c-di-AMP accumulation also impaired cell envelope integrity. An L. monocytogenes mutant deleted for c-di-AMP phosphodiesterases (pdeA pgpH mutant) exhibited a 4-fold increase in c-di-AMP levels and several cell wall defects. For instance, the pdeA pgpH mutant was defective for the synthesis of peptidoglycan muropeptides and was susceptible to cell wall-targeting antimicrobials. Among different muropeptide precursors, we found that the pdeA pgpH strain was particularly impaired in the synthesis of d-Ala-d-Ala, which is required to complete the pentapeptide stem associs might be an important mechanism for attenuated virulence in bacteria with high c-di-AMP levels.
  Phyllodes tumours (PTs) are rare fibroepithelial tumours accounting for <1% of all breast tumours. We assessed clinicopathological features and their prognostic effect in a single-institution patients' cohort.
 
  Patients diagnosed with PT between 2001 and 2018 at our institution were identified.  https://www.selleckchem.com/products/jte-013.html  Clinical, surgical and pathological features were collected. Phyllodes-related relapse was defined as locoregional or distant recurrence (contralateral excluded), whichever first.
 
  A total of 166 patients were included 115 with benign, 30 with borderline and 21 with malignant PTs. Features associated with malignant PT were younger age, larger T size, higher mitotic count, marked cytological atypia, stromal overgrowth, stromal hypercellularity, necrosis and heterologous differentiation (all p<0.01). The majority of patients with malignant PT underwent mastectomy (63.2% vs 3% of benign/borderline, p<0.001) and had negative surgical margins (83.3%). 4-year cumulative phyllodes-related relapse incidence was 7% was associated with an increased risk of phyllodes-related relapse in benign PT.
 Patients with malignant PT had increased rates of phyllodes-related relapse and phyllodes-related death. Cellular atypia and heterologous differentiation were poor prognostic factors in the entire cohort; large tumour size was associated with an increased risk of phyllodes-related relapse in benign PT.
  Data regarding breast cancer epidemiology, treatment and survival in Africa are scarce. We aimed to assess the distribution of breast cancer subtypes in Mozambique and its impact on patients' treatment and survival. The concordance of biomarker assessment between cytological and histological samples was also evaluated.
 
  Prospective cohort study including 210 patients diagnosed between January 2015 and August 2017, followed to November 2019. Clinicopathological characteristics, treatment, 3-year overall survival (OS) and disease-free survival (DFS) were compared across classic tumour subtypes (oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive and triple-negative breast cancer (TNBC)) and surrogate intrinsic subtypes (St. Gallen classification). Concordance was measured using Cohen's κ statistics.
 
  A total of 51% of patients had ER-positive/HER2-negative tumours, 24% HER2-positive and 25% TNBC. Concordance between cytological and histological samples renegative patients, partly due to the limited treatment options. A systematic assessment of ER, PR and HER2 status is feasible and may help tailoring and optimise the treatment of patients with breast cancer in low-resource settings, potentially leading to survival gains in this underserved population.
 There was a high proportion of HER2-positive and TNBC among Mozambican patients and their survival was poor compared with ER-positive/HER2-negative patients, partly due to the limited treatment options. A systematic assessment of ER, PR and HER2 status is feasible and may help tailoring and optimise the treatment of patients with breast cancer in low-resource settings, potentially leading to survival gains in this underserved population.The role of the ventromedial prefrontal cortex (vmPFC) in human pavlovian threat conditioning has been relegated largely to the extinction or reversal of previously acquired stimulus-outcome associations. However, recent neuroimaging evidence questions this view by also showing activity in the vmPFC during threat acquisition. Here we investigate the casual role of vmPFC in the acquisition of pavlovian threat conditioning by assessing skin conductance response (SCR) and declarative memory of stimulus-outcome contingencies during a differential pavlovian threat-conditioning paradigm in eight patients with a bilateral vmPFC lesion, 10 with a lesion outside PFC and 10 healthy participants (each group included both females and males). Results showed that patients with vmPFC lesion failed to produce a conditioned SCR during threat acquisition, despite no evidence of compromised SCR to unconditioned stimulus or compromised declarative memory for stimulus-outcome contingencies. These results suggest that the vmPFC plays a causal role in the acquisition of new learning and not just in the extinction or reversal of previously acquired learning, as previously thought.