The hyperarid mangrove in the Middle East is characterised by the absence of rivers or freshwater inputs and is one of the most extreme settings of this ecosystem on Earth. Endemic to Qatar's ...hyperarid mangroves, a Palaemon shrimp is uniquely confined to a sole mangrove site in the Arabian Gulf. Within these mangrove channels, we unveiled brine groundwater sources exceeding 70 ppt salinity, contrasting the local marine standard of 42 ppt. Concurrently, a mysid species typically linked to salt pans and groundwater coexists. Stable isotopic analysis implied the existence of a predator-prey dynamic between this mysid species and the studied shrimp. Then, investigating the endemic shrimp's adaptation to extreme salinity, we conducted osmolarity experiments and phylogenetic studies. Our findings demonstrate that this shrimp transitions from hypo- to hyper-osmoregulation, tolerating salinities from 18 to 68 ppt-an unprecedented osmoregulatory capacity among caridean shrimps. This speciation pattern likely arises from the species osmolarity adaptation, as suggested for other Palaemon congeners. Phylogenetic analysis of the studied Palaemon, along with the mangrove's geological history, suggests a profound evolutionary interplay between the ecosystem and the shrimp since the Eocene. This study proposes the hyperarid mangrove enclave as an Athalassic mangrove oasis-a distinctive, isolated ecosystem within the desert landscape.
Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled the NK cell ...response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56
population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56
NK cells, including decreased expression of PLZF and the Fc receptor γ-chain, increased histone methylation, and increased protein expression of LAG-3, KIR, and LILRB1. CD56
NK cells were highly functional and displayed greater antibody-dependent cellular cytotoxicity than CD56
NK cells. Higher frequencies of CD56
NK cells were associated with protection against symptomatic malaria and high parasite densities. After marked reductions in malaria transmission, frequencies of these cells rapidly declined, suggesting that continuous exposure to
is required to maintain this modified, adaptive-like NK cell subset.
Germinal centers (GCs) form in secondary lymphoid organs in response to infection and immunization and are the source of affinity-matured B cells. The duration of GC reactions spans a wide range, and ...long-lasting GCs (LLGCs) are potentially a source of highly mutated B cells. We show that rather than consisting of continuously evolving B cell clones, LLGCs elicited by influenza virus or SARS-CoV-2 infection in mice are sustained by progressive replacement of founder clones by naive-derived invader B cells that do not detectably bind viral antigens. Rare founder clones that resist replacement for long periods are enriched in clones with heavily mutated immunoglobulins, including some with very high affinity for antigen, that can be recalled by boosting. Our findings reveal underappreciated aspects of the biology of LLGCs generated by respiratory virus infection and identify clonal replacement as a potential constraint on the development of highly mutated antibodies within these structures.
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•Influenza infection induces long-lived germinal centers (LLGCs)•LLGCs are composed of “founder” and naive “invader” cells•Invaders are not flu specific but compete with founders for affinity maturation•Late founder clones export highly mutated memory cells that can be recalled
B cells continue to hone their affinity for antigen in lymph-node germinal centers long after an initial respiratory virus infection, but as time goes on, new B cells that are less specific come to dominate the population. This work suggests that there are limits to how much a germinal-center reaction can hone the B cell and antibody repertoire over time.
Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory ...failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000.
Tumor necrosis factor (TNF)-α is produced by macrophages and other cells, and is believed to participate in granulomatous inflammation. Targeted antagonism of TNF-α has been proposed as a novel ...treatment strategy for sarcoidosis. Etanercept is a dimeric fusion protein that binds specifically to TNF-α, rendering it biologically inactive.
To assess whether etanercept has potential efficacy in the treatment of progressive pulmonary sarcoidosis.
Prospective, open-label, phase-2 treatment trial.
Mayo Clinic, Rochester, MN.
Stage II or III progressive pulmonary sarcoidosis.
Etanercept, 25 mg subcutaneously twice weekly.
Pulmonary function, chest radiographs, dyspnea, and TNF-α levels in serum and BAL fluid.
The study was terminated after the enrollment of 17 patients due to an early-stop clause of the pretrial study design related to excessive treatment failures. Neither absolute levels of TNF-α nor TNF-α activity in the serum, BAL fluid, or alveolar macrophages were able to predict which patients would respond to etanercept.
In patients with progressive stage II or III pulmonary sarcoidosis, etanercept was frequently associated with early or late treatment failure. These data would not support the design of a large multicenter randomized trial comparing etanercept with conventional corticosteroid therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neutralizing antibodies have been shown to develop rapidly following SARS-CoV-2 infection, specifically against spike (S) protein, where cytokine release and production is understood to drive the ...humoral immune response during acute infection. Thus, we evaluated the quantity and function of antibodies across disease severities and analyzed the associated inflammatory and coagulation pathways to identify acute markers that correlate with antibody response following infection.
Blood samples were collected from patients at time of diagnostic SARS-CoV-2 PCR testing between March 2020-November 2020. Plasma samples were analyzed using the MesoScale Discovery (MSD) Platform using the COVID-19 Serology Kit and U-Plex 8 analyte multiplex plate to measure anti-alpha and beta coronavirus antibody concentration and ACE2 blocking function, as well as plasma cytokines.
A total of 230 (181 unique patients) samples were analyzed across the 5 COVID-19 disease severities. We found that antibody quantity directly correlated with functional ability to block virus binding to membrane-bound ACE2, where a lower SARS-CoV-2 anti-spike/anti-RBD response corresponded with a lower antibody blocking potential compared to higher antibody response (anti-S1 r = 0.884,
< 0.001; anti-RBD r = 0.75,
< 0.001). Across all the soluble proinflammatory markers we examined, ICAM, IL-1β, IL-4, IL-6, TNFα, and Syndecan showed a statistically significant positive correlation between cytokine or epithelial marker and antibody quantity regardless of COVID-19 disease severity. Analysis of autoantibodies against type 1 interferon was not shown to be statistically significant between disease severity groups.
Previous studies have shown that proinflammatory markers, including IL-6, IL-8, IL-1β, and TNFα, are significant predictors of COVID-19 disease severity, regardless of demographics or comorbidities. Our study demonstrated that not only are these proinflammatory markers, as well as IL-4, ICAM, and Syndecan, correlative of disease severity, they are also correlative of antibody quantity and quality following SARS-CoV-2 exposure.
Bromeliad phytotelmata are habitats for different organisms and models for ecological studies. Although poorly known, these environments are widely distributed in tropical ecosystems, harboring ...cosmopolitan and endemic species. Here, we investigated the diversity of the eukaryotic community in bromeliad phytotelmata considering the influence of altitude. We randomly sampled three bromeliad individuals (twice per season over one year) at four altitudinal strata (20 m, 400 m, 910 m, and 915 m) through a mountain range in southern Brazil. Species richness of phytotelmata community was higher at intermediate altitude while community-wide multivariate analyses revealed differences in phytotelmata communities at each height. Winter was the season with highest community richness, but a peak in summer was observed. Diversity partitioning in different spatial components showed that gamma diversity decreased linearly with altitude, whereas alpha diversity peaked at intermediate altitudes, and beta diversity decreased with height. The relative importance of the components of beta diversity showed different patterns according to the altitude: turnover was more important at intermediate and lower levels, while higher altitude communities were more nested. Our results indicate that differences in height affect diversity patterns of bromeliad phytotelmata communities, which were more diverse at lower altitudes in comparison with more homogeneous communities at higher levels.
The parasitic copepod
Gauchergasilus euripedesi
(Montú, 1980) Montú & Boxshall, 2002 was described from plankton samples and specimens found in four fish species from the estuarine area of Patos ...Lagoon, state of Rio Grande do Sul (RS), Brazil. Later, one different fish species was reported parasitized with
G. euripedesi
in the same locality. Species of
Astyanax
Baird & Girard, 1854 (
Astyanax henseli
Melo & Buckup, 2006 and
Astyanax lacustris
(Lütken, 1875)) and
Psalidodon
Eigenmann, 1911 (
Psalidodon eigenmanniorum
(Cope, 1894) and Psalidodon aff. fasciatus (Cuvier, 1819)) were collected in two environments (Pintada Island, municipality of Porto Alegre and Itapeva Lagoon, municipality of Terra de Areia, RS) to investigate their parasites. The copepods found in the gill arches were counted, processed, mounted in permanent slides, and photographed using light microscopy, or processed for observation in scanning electron microscopy. Specimens of
P. eigenmanniorum
from Pintada Island,
A. lacustris
and P. aff. fasciatus from Itapeva Lagoon, were parasitized by
G. euripedesi
, with prevalences of 29.03% (
A. lacustris
), 10.34% (
P. eigenmanniorum
), and 9.68% (P. aff. fasciatus). Measurements obtained for specimens of
G. euripedesi
were similar to those found in the literature, except for egg sacs which were larger in the specimens examined in the present study. In addition to being the first report of
G. euripedesi
parasitizing species of fish (
A. lacustris
,
P. eigenmanniorum
, and P. aff. fasciatus), the results presented here also extend the known geographic distribution of the copepod species.
We describe a 29-year-old woman who presented with chronic pleuropericarditis complicated by lung entrapment and constrictive pericarditis. Pleural biopsy performed during the decortication procedure ...revealed fibrinous pleuritis with lymphoplasmacytic inflammation including IgG4-positive plasma cells. The patient responded favorably to corticosteroid therapy with resolution of pleural effusion and constrictive physiology. To our knowledge, this is the first reported case of IgG4-related systemic disease manifesting as lung entrapment and constrictive pericarditis.
Caspases are the major executioners of cell death, serving as molecular guillotines to behead many proteins required for maintenance of cellular homeostasis. Identification of caspase substrates has ...taken on increasing importance as we attempt to better understand the molecular mechanisms involved in regulating the struggle between life and death. Many caspase substrates have been described and include RNA binding proteins such as La and U1-70 kD, structural proteins such as keratin and nuclear lamins, and transcription factors or their regulatory proteins that include IkappaB, SP1, and SREBP. Kinases and other signaling proteins are perfectly suited to regulate life and death decisions in response to cellular stressors and have only recently been identified as important caspase substrates. Here we review the current status of signaling pathways that are activated, inactivated or dysregulated by proteases such as caspases and calpain to control entry into apoptosis. The emerging concept that some caspase pathways may be inhibited by cellular and viral apoptosis inhibitory proteins while other caspase pathways are preserved suggests that a subset of these kinases may exist as cleaved 'isoforms' in cells that are not destined to perish. By acting as executioners and as important 'molecular sensors' of the degree of cellular injury, the signaling proteins described in this review are strong candidates to mediate downstream events, both in condemned and in viable cells.
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