Stem cell ageing underlies the ageing of tissues, especially those with a high cellular turnover. There is growing evidence that the ageing of the immune system is initiated at the very top of the ...haematopoietic hierarchy and that the ageing of haematopoietic stem cells (HSCs) directly contributes to changes in the immune system, referred to as immunosenescence. In this Review, we summarize the phenotypes of ageing HSCs and discuss how the cell-intrinsic and cell-extrinsic mechanisms of HSC ageing might promote immunosenescence. Stem cell ageing has long been considered to be irreversible. However, recent findings indicate that several molecular pathways could be targeted to rejuvenate HSCs and thus to reverse some aspects of immunosenescence.
Paired associative stimulation (PAS) can increase motor cortical excitability, possibly by long-term potentiation (LTP)-like mechanisms. As the capability of the cortex for plasticity decreases with ...age, we were interested here in testing interindividual variability and age-dependency of the PAS effect. Motor-evoked potentials (MEPs) were recorded from the resting right
abductor pollicis brevis
muscle before and for 30 min after PAS in 27 healthy subjects (22–71 years of age). PAS consisted of 225 pairs (rate, 0.25 Hz) of right median nerve stimulation followed at an interval equaling the individual N20-latency of the median nerve somatosensory-evoked cortical potential plus 2 ms by transcranial magnetic stimulation of the hand area of left primary motor cortex (PAS
N20+2
). The PAS
N20+2
-induced changes in MEP amplitude (ratio post PAS/pre PAS) were highly variable (1.00 ± 0.07, range 0.36–1.68). Fourteen subjects showed the expected LTP-like MEP increase (responders) while 13 subjects showed a long-term depression (LTD)-like MEP decrease (non-responders). Responders had a significantly lower resting motor threshold (RMT) and minimum stimulus intensity to elicit MEPs of 1 mV (MEP
1 mV
) than non-responders. RMT and MEP
1 mV
correlated significantly negatively with the PAS
N20+2
effect. The absolute PAS
N20+2
effect size irrespective of its direction decreased with age (
r
= −0.57,
P
= 0.002), i.e., LTP-like and LTD-like plasticity were large in young subjects but substantially smaller in elderly subjects. In conclusion, measures of motor cortical excitability (RMT, MEP
1 mV
) and age determine direction and magnitude of PAS effects in individual subjects.
Plant-parasitic nematodes are destructive pests causing losses of billions of dollars annually. An effective plant defence against pathogens relies on the recognition of pathogen-associated molecular ...patterns (PAMPs) by surface-localised receptors leading to the activation of PAMP-triggered immunity (PTI). Extensive studies have been conducted to characterise the role of PTI in various models of plant-pathogen interactions. However, far less is known about the role of PTI in roots in general and in plant-nematode interactions in particular. Here we show that nematode-derived proteinaceous elicitor/s is/are capable of inducing PTI in Arabidopsis in a manner dependent on the common immune co-receptor BAK1. Consistent with the role played by BAK1, we identified a leucine-rich repeat receptor-like kinase, termed NILR1 that is specifically regulated upon infection by nematodes. We show that NILR1 is essential for PTI responses initiated by nematodes and nilr1 loss-of-function mutants are hypersusceptible to a broad category of nematodes. To our knowledge, NILR1 is the first example of an immune receptor that is involved in induction of basal immunity (PTI) in plants or in animals in response to nematodes. Manipulation of NILR1 will provide new options for nematode control in crop plants in future.
Both in the community and hospital setting, urinary tract infections (UTIs) are common. Initial appropriate empirical treatment requires a good knowledge of epidemiological data. In this review, the ...most recent global epidemiological data of UTIs have been summarized.
Community-associated UTI (CAUTI) prevalence is 0.7% and the main risk factors are age, history of UTI, sexual activity and diabetes. The most common pathogen is Escherichia coli and resistance rates to common antibiotics depend very much on the geographical location. The lowest observed resistance was for fosfomycin (range: 0-2.9%), nitrofurantoin (range: 0-4.4%) and mecillinam (range: 0-4%). Healthcare-associated UTI (HAUTI) frequency among HCAIs is 12.9 (confidence interval: 10.2-16%), 19.6 and 24% in the United States, Europe and developing countries, respectively. In urology departments, the prevalence is 5.1%. Resistance to almost all antibiotics in HAUTIs is above 20% and there is a significant geographical variation. Community onset HAUTIs bacterial spectrum is similar to hospital onset HAUTIs and different from CAUTIs.
It is challenging to provide with an exact frequency of UTIs. Both CAUTI and HAUTI frequency, pathogen spectrum and resistance rates vary according to geographical setting.
With the rapid progression of additive manufacturing and the emergence of new 3D printing technologies, accuracy assessment is mostly being performed on isosymmetric test bodies. However, the ...accuracy of anatomic models can vary. The dimensional accuracy of root mean square values in terms of trueness and precision of 50 mandible replicas, printed with five common printing technologies, were evaluated. The highest trueness was found for the selective laser sintering printer (0.11 ± 0.016 mm), followed by a binder jetting printer (0.14 ± 0.02 mm), and a fused filament fabrication printer (0.16 ± 0.009 mm). However, highest precision was identified for the fused filament fabrication printer (0.05 ± 0.005 mm) whereas other printers had marginally lower values. Despite the statistically significance (
< 0.001), these differences can be considered clinically insignificant. These findings demonstrate that all 3D printing technologies create models with satisfactory dimensional accuracy for surgical use. Since satisfactory results in terms of accuracy can be reached with most technologies, the choice should be more strongly based on the printing materials, the intended use, and the overall budget. The simplest printing technology (fused filament fabrication) always scored high and thus is a reliable choice for most purposes.
The actin-related protein (Arp)2/3 complex nucleates branched actin filament networks pivotal for cell migration, endocytosis and pathogen infection. Its activation is tightly regulated and involves ...complex structural rearrangements and actin filament binding, which are yet to be understood. Here, we report a 9.0 Å resolution structure of the actin filament Arp2/3 complex branch junction in cells using cryo-electron tomography and subtomogram averaging. This allows us to generate an accurate model of the active Arp2/3 complex in the branch junction and its interaction with actin filaments. Notably, our model reveals a previously undescribed set of interactions of the Arp2/3 complex with the mother filament, significantly different to the previous branch junction model. Our structure also indicates a central role for the ArpC3 subunit in stabilizing the active conformation.
UTIs are amongst the most frequent bacterial infections. However, the clinical phenotypes of UTI are heterogeneous and range from rather benign, uncomplicated infections to complicated UTIs (cUTIs), ...pyelonephritis and severe urosepsis. Stratification of patients with UTIs is, therefore, important. Several classification systems exist for the description and classification of UTIs, with the common rationale that cUTIs have a higher risk of recurrence or chronification, progression or severe outcome than uncomplicated UTIs. The pathophysiology and treatment of cUTIs and pyelonephritis are driven more by host factors than by pathogen attributes. cUTIs and pyelonephritis are associated with high antimicrobial resistance rates among causative pathogens. However, antimicrobial resistance rates can differ substantially, depending on the population being studied and whether the data being analysed are from surveillance studies, registry data or interventional studies, in which specific inclusion and exclusion criteria are used for patient selection. For example, antibiotic resistance rates are higher in patients with urosepsis than in those with less severe infections. Thus, treatment outcomes differ substantially among studies, ranging from 50% to almost 100% clearance of infection, depending on the patient population analysed, the UTI entities included and the primary outcome of the study. Pyelonephritis and cUTIs have emerged as infection models for the study of novel antibiotics, including extensive investigation of novel substances active against Gram-negative bacteria.
Antibiotic resistance is a threat to public health, and uncomplicated urinary tract infections (uUTIs) are an example of this concern. This systematic review (International Prospective Register of ...Systematic Reviews PROSPERO ID: CRD42020156674) is the first to determine the prevalence of
resistance to fluoroquinolones in women with community-acquired uUTI. PubMed and Embase searches were conducted; 38 studies fulfilled eligibility criteria and were included in the systematic review. Within Europe, ciprofloxacin resistance in
isolates varied between countries and increased in some from 2006 to 2008 and 2014 to 2016, specifically in the United Kingdom (0.5% to 15.3%), Germany (8.7% to 15.1%), and Spain (22.9% to 30.8%), although methodologies and settings were often not comparable. In Asia, there was a substantial increase in ciprofloxacin resistance during 2008 to 2014 from 25% to more than 40%. In North America, resistance to ciprofloxacin also increased between 2008 and 2017, from 4% to 12%. Data exploring different age groups did not show a consistent relationship with resistance, whereas two studies found that fluoroquinolone resistance was higher in postmenopausal women than premenopausal women. One study indicated a link between fluoroquinolone resistance and uUTI recurrence. These findings may have implications for the empirical treatment of uUTI with fluoroquinolones globally, but more data are needed to fully understand regional situations and impact patient management.
We present a compact sensor for carbon monoxide (CO) in air and exhaled breath based on a room temperature interband cascade laser (ICL) operating at 4.69 µm, a low-volume circular multipass cell and ...wavelength modulation absorption spectroscopy. A fringe-limited (1σ) sensitivity of 6.5 × 10
cm
Hz
and a detection limit of 9 ± 5 ppbv at 0.07 s acquisition time are achieved, which constitutes a 25-fold improvement compared to direct absorption spectroscopy. Integration over 10 s increases the precision to 0.6 ppbv. The setup also allows measuring the stable isotope
CO in breath. We demonstrate quantification of indoor air CO and real-time detection of CO expirograms from healthy non-smokers and a healthy smoker before and after smoking. Isotope ratio analysis indicates depletion of
CO in breath compared to natural abundance.
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