An unexpected evolution of symptomatic mild middle cerebral artery (MCA) stenosis: asymptomatic occlusion

<p>Abstract</p> <p>Background</p> <p>The intracranial localization of large artery disease is recognized as the main cause of ischemic stroke in the world, considering all countries, although its global burden is widely underestimated. Indeed it has been reported more frequently in Asians and African-American people, but the finding of intracranial stenosis as a cause of ischemic stroke is relatively common also in Caucasians. The prognosis of patients with stroke due to intracranial steno-occlusion is strictly dependent on the time of recanalization. Moreover, the course of the vessel involvement is highly dynamic in both directions, improvement or worsening, although several data are derived from the atherosclerotic subtype, compared to other causes.</p> <p>Case description</p> <p>We report the clinical, neurosonological and neuroradiological findings of a young woman, who came to our Stroke Unit because of the abrupt onset of aphasia during her work. An urgent neurosonological examination showed a left M1 MCA stenosis, congruent with the presenting symptoms; magnetic resonance imaging confirmed this finding and identified an acute ischemic lesion on the left MCA territory. The past history of the patient was significant only for a hyperinsulinemic condition, treated with metformine, and a mild overweight. At this time a selective cerebral angiography was not performed because of the patient refusal and she was discharged on antiplatelet and lipid-lowering therapy, having failed to identify autoimmune or inflammatory diseases. Within 1 month, she went back to our attention because of the recurrence of aphasia, lasting about ten minutes. Neuroimaging findings were unchanged, but the patient accepted to undergo a selective cerebral angiography, which showed a mild left distal M1 MCA stenosis.</p> <p>During the follow-up the patient did not experienced any recurrence, but a routine neurosonological examination found an unexpected evolution of the known MCA stenosis, i.e. left M1 MCA occlusion. Neuroradiological imaging did not identify new lesions of the brain parenchyma and a repeated selective cerebral angiography confirmed the left M1 MCA occlusion.</p> <p>Conclusions</p> <p>Regardless of the role of metabolic and/or inflammatory factors on the aetiology of the intracranial stenosis in this case, the course of the vessel disease was unexpected and previously unreported in the literature at our knowledge.</p

CAPERS-LRD-z9: A Gas-enshrouded Little Red Dot Hosting a Broad-line Active Galactic Nucleus at z = 9.288

We present CAPERS-LRD-z9, a little red dot (LRD) that we confirm to be a z = 9.288 broad-line active galactic nucleus (BLAGN). First identified as a high-redshift LRD candidate from PRIMER NIRCam photometry, follow-up NIRSpec/PRISM spectroscopy of CAPERS-LRD-z9 from the CANDELS-Area Prism Epoch of Reionization Survey (CAPERS) has revealed a broad 3500 km s−1 full width at half-maximum Hβ emission line and narrow [O iii] λλ4959, 5007 lines, indicative of a BLAGN. Based on the broad Hβ line, we compute a canonical black hole mass of log ( M BH / M ⊙ ) = 7.58 ± 0.15 , although full consideration of systematic uncertainties yields a conservative range of 6.65 10 cm−3) neutral gas. We model CAPERS-LRD-z9 using Cloudy to fit the emission redward of the Balmer break with a dense-gas-enshrouded AGN and bagpipes to fit the rest-ultraviolet emission as a host-galaxy stellar population. This upper limit on the stellar mass of the host galaxy (9 M⊙) implies that the black hole to stellar mass ratio may be extremely large, possibly >5% (although systematic uncertainties on the black hole mass prevent strong conclusions). However, the shape of the UV continuum differs from typical high-redshift star-forming galaxies, indicating that this UV emission may also be of AGN origin; hence, the true stellar mass of the host may be still lower

BosR (BB0647) Controls the RpoN-RpoS Regulatory Pathway and Virulence Expression in Borrelia burgdorferi by a Novel DNA-Binding Mechanism

In Borrelia burgdorferi (Bb), the Lyme disease spirochete, the alternative σ factor σ54 (RpoN) directly activates transcription of another alternative σ factor, σS (RpoS) which, in turn, controls the expression of virulence-associated membrane lipoproteins. As is customary in σ54-dependent gene control, a putative NtrC-like enhancer-binding protein, Rrp2, is required to activate the RpoN-RpoS pathway. However, recently it was found that rpoS transcription in Bb also requires another regulator, BosR, which was previously designated as a Fur or PerR homolog. Given this unexpected requirement for a second activator to promote σ54-dependent gene transcription, and the fact that regulatory mechanisms among similar species of pathogenic bacteria can be strain-specific, we sought to confirm the regulatory role of BosR in a second virulent strain (strain 297) of Bb. Indeed, BosR displayed the same influence over lipoprotein expression and mammalian infectivity for strain Bb 297 that were previously noted for Bb strain B31. We subsequently found that recombinant BosR (rBosR) bound to the rpoS gene at three distinct sites, and that binding occurred despite the absence of consensus Fur or Per boxes. This led to the identification of a novel direct repeat sequence (TAAATTAAAT) critical for rBosR binding in vitro. Mutations in the repeat sequence markedly inhibited or abolished rBosR binding. Taken together, our studies provide new mechanistic insights into how BosR likely acts directly on rpoS as a positive transcriptional activator. Additional novelty is engendered by the facts that, although BosR is a Fur or PerR homolog and it contains zinc (like Fur and PerR), it has other unique features that clearly set it apart from these other regulators. Our findings also have broader implications regarding a previously unappreciated layer of control that can be involved in σ54–dependent gene regulation in bacteria

Role of Acetyl-Phosphate in Activation of the Rrp2-RpoN-RpoS Pathway in Borrelia burgdorferi

Borrelia burgdorferi, the Lyme disease spirochete, dramatically alters its transcriptome and proteome as it cycles between the arthropod vector and mammalian host. During this enzootic cycle, a novel regulatory network, the Rrp2-RpoN-RpoS pathway (also known as the σ54–σS sigma factor cascade), plays a central role in modulating the differential expression of more than 10% of all B. burgdorferi genes, including the major virulence genes ospA and ospC. However, the mechanism(s) by which the upstream activator and response regulator Rrp2 is activated remains unclear. Here, we show that none of the histidine kinases present in the B. burgdorferi genome are required for the activation of Rrp2. Instead, we present biochemical and genetic evidence that supports the hypothesis that activation of the Rrp2-RpoN-RpoS pathway occurs via the small, high-energy, phosphoryl-donor acetyl phosphate (acetyl∼P), the intermediate of the Ack-Pta (acetate kinase-phosphate acetyltransferase) pathway that converts acetate to acetyl-CoA. Supplementation of the growth medium with acetate induced activation of the Rrp2-RpoN-RpoS pathway in a dose-dependent manner. Conversely, the overexpression of Pta virtually abolished acetate-induced activation of this pathway, suggesting that acetate works through acetyl∼P. Overexpression of Pta also greatly inhibited temperature and cell density-induced activation of RpoS and OspC, suggesting that these environmental cues affect the Rrp2-RpoN-RpoS pathway by influencing acetyl∼P. Finally, overexpression of Pta partially reduced infectivity of B. burgdorferi in mice. Taken together, these findings suggest that acetyl∼P is one of the key activating molecule for the activation of the Rrp2-RpoN-RpoS pathway and support the emerging concept that acetyl∼P can serve as a global signal in bacterial pathogenesis

Comparison of Human and Soil Candida tropicalis Isolates with Reduced Susceptibility to Fluconazole

Infections caused by treatment-resistant non-albicans Candida species, such as C. tropicalis, has increased, which is an emerging challenge in the management of fungal infections. Genetically related diploid sequence type (DST) strains of C. tropicalis exhibiting reduced susceptibility to fluconazole circulated widely in Taiwan. To identify the potential source of these wildly distributed DST strains, we investigated the possibility of the presence in soil of such C. tropicalis strains by pulsed field gel electrophoresis (PFGE) and DST typing methods. A total of 56 C. tropicalis isolates were recovered from 26 out of 477 soil samples. Among the 18 isolates with reduced susceptibility to fluconazole, 9 belonged to DST149 and 3 belonged to DST140. Both DSTs have been recovered from our previous studies on clinical isolates from the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) program. Furthermore, these isolates were more resistant to agricultural azoles. We have found genetically related C. tropicalis exhibiting reduced susceptibility to fluconazole from the human hosts and environmental samples. Therefore, to prevent patients from acquiring C. tropicalis with reduced susceptibility to azoles, prudent use of azoles in both clinical and agricultural settings is advocated

The COSMOS-Web Lens Survey(COWLS) III: forecasts versus data

\ua9 The Author(s) 2025. Published by Oxford University Press on behalf of Royal Astronomical Society.We compare forecasts for the abundance and properties of strong gravitational lenses in the COSMOS-Web survey, a 0.54 deg2 survey of the COSMOS field using the NIRCam and MIRI instruments aboard James Webb Space Telescope (JWST), with the first catalogue of strong lens candidates identified in the observed NIRCam data, COWLS. We modify the lenspop package to produce a forecast for strong lensing in COSMOS-Web. We add a new mock galaxy catalogue to use as the source population, as well as the COSMOS-Web survey specifications, including the transmission data for the four NIRCam filters used. We forecast 107 strong lenses can be detected in COSMOS-Web across all bands, assuming complete subtraction of the lens galaxy light. The majority of the lenses are forecast to have small Einstein radii (θE &lt; 1$ arcsec) and lie at redshifts in the range 0 &lt; z &lt; 2, while the source redshift distribution peaks at z ~ 3 and has a long tail extending up to z ~ 11, unambiguously showing that strong lensing in JWST can probe the entirety of the epoch of reionization. We compare our forecast with the distributions of Einstein radii, lens photometric redshifts, and lens and source magnitudes in the observed lenses, finding that while the forecast and observed Einstein radii distributions match, the redshifts and magnitudes do not. The observed lens redshift distribution peaks at a slightly lower redshift than the forecast one, while the lens magnitudes are systematically brighter in the observed data than in the forecast

Elevation in Body Temperature to Fever Range Enhances and Prolongs Subsequent Responsiveness of Macrophages to Endotoxin Challenge

Macrophages are often considered the sentries in innate immunity, sounding early immunological alarms, a function which speeds the response to infection. Compared to the large volume of studies on regulation of macrophage function by pathogens or cytokines, relatively little attention has been devoted to the role of physical parameters such as temperature. Given that temperature is elevated during fever, a long-recognized cardinal feature of inflammation, it is possible that macrophage function is responsive to thermal signals. To explore this idea, we used LPS to model an aseptic endotoxin-induced inflammatory response in BALB/c mice and found that raising mouse body temperature by mild external heat treatment significantly enhances subsequent LPS-induced release of TNF-α into the peritoneal fluid. It also reprograms macrophages, resulting in sustained subsequent responsiveness to LPS, i.e., this treatment reduces “endotoxin tolerance” in vitro and in vivo. At the molecular level, elevating body temperature of mice results in a increase in LPS-induced downstream signaling including enhanced phosphorylation of IKK and IκB, NF-κB nuclear translocation and binding to the TNF-α promoter in macrophages upon secondary stimulation. Mild heat treatment also induces expression of HSP70 and use of HSP70 inhibitors (KNK437 or Pifithrin-µ) largely abrogates the ability of the thermal treatment to enhance TNF-α, suggesting that the induction of HSP70 is important for mediation of thermal effects on macrophage function. Collectively, these results support the idea that there has been integration between the evolution of body temperature regulation and macrophage function that could help to explain the known survival benefits of fever in organisms following infection

Cyclic di-GMP is Essential for the Survival of the Lyme Disease Spirochete in Ticks

Cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1), which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol). To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host