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The archaeal cell envelope
Key Points
The cell envelope of archaea is fundamentally different from bacteria in that it does not contain peptidoglycan, and archaeal membranes are composed of ether lipids instead of ester lipids.
Most archaea are surrounded by a surface-layer (S-layer), which is a proteinaceous two-dimensional crystal layer. Some archaeal cell envelopes contain pseudomurein or other unique sugar polymers.
Most of the extracellular archaeal proteins are glycosylated (
N
-linked,
O
-linked or both). The archaeal
N
-glycosylation pathway bears similar features to both the eukaryotic and the bacterial pathway. The known archaeal
N
-glycans are exceedingly diverse in their composition and structure.
Most archaeal pili and all archaeal flagella studied to date are assembled by simple type IV pilin-like machineries.
The archaeal cell surface is home to a range of lipids, proteins, polysaccharides and surface structures that are distinct from those observed at the bacterial cell surface. In this Review, Albers and Meyer discuss our current understanding of the composition of the archaeal cell envelope.
At first glance, archaea and bacteria look alike; however, the composition of the archaeal cell envelope is fundamentally different from the bacterial cell envelope. With just one exception, all archaea characterized to date have only a single membrane and most are covered by a paracrystalline protein layer. This Review discusses our current knowledge of the composition of the archaeal cell surface. We describe the wide range of cell wall polymers,
O
- and
N
-glycosylated extracellular proteins and other cell surface structures that archaea use to interact with their environment.
Journal Article
Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study
Over 40 000 patients with COVID-19 have been hospitalised in New York City (NY, USA) as of April 28, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed.
This prospective observational cohort study took place at two NewYork-Presbyterian hospitals affiliated with Columbia University Irving Medical Center in northern Manhattan. We prospectively identified adult patients (aged ≥18 years) admitted to both hospitals from March 2 to April 1, 2020, who were diagnosed with laboratory-confirmed COVID-19 and were critically ill with acute hypoxaemic respiratory failure, and collected clinical, biomarker, and treatment data. The primary outcome was the rate of in-hospital death. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal replacement therapy, and time to in-hospital clinical deterioration following admission. The relation between clinical risk factors, biomarkers, and in-hospital mortality was modelled using Cox proportional hazards regression. Follow-up time was right-censored on April 28, 2020 so that each patient had at least 28 days of observation.
Between March 2 and April 1, 2020, 1150 adults were admitted to both hospitals with laboratory-confirmed COVID-19, of which 257 (22%) were critically ill. The median age of patients was 62 years (IQR 51–72), 171 (67%) were men. 212 (82%) patients had at least one chronic illness, the most common of which were hypertension (162 [63%]) and diabetes (92 [36%]). 119 (46%) patients had obesity. As of April 28, 2020, 101 (39%) patients had died and 94 (37%) remained hospitalised. 203 (79%) patients received invasive mechanical ventilation for a median of 18 days (IQR 9–28), 170 (66%) of 257 patients received vasopressors and 79 (31%) received renal replacement therapy. The median time to in-hospital deterioration was 3 days (IQR 1–6). In the multivariable Cox model, older age (adjusted hazard ratio [aHR] 1·31 [1·09–1·57] per 10-year increase), chronic cardiac disease (aHR 1·76 [1·08–2·86]), chronic pulmonary disease (aHR 2·94 [1·48–5·84]), higher concentrations of interleukin-6 (aHR 1·11 [95%CI 1·02–1·20] per decile increase), and higher concentrations of D-dimer (aHR 1·10 [1·01–1·19] per decile increase) were independently associated with in-hospital mortality.
Critical illness among patients hospitalised with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extrapulmonary organ dysfunction, and substantial in-hospital mortality.
National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health, and the Columbia University Irving Institute for Clinical and Translational Research.
Journal Article
Prevalence and characterisation of band-shaped tail lesions in Holstein cows
The aim of the study was to characterise and determine the prevalence of band-shaped tail lesions in Holstein cows. Lesions were present either as wounds or by epithelised granulation/connective tissue formations. Both types were characterised by a median localisation 7 cm from the tip of the tail, and they occurred on the dorsal aspect of the tail. From here they encircled the tail either completely or in varying degrees, and they were often present as isolated lesions (93%). The prevalence of band-shaped tail lesions was found to be 25% among 2099 cows examined in 16 Danish Holstein herds with a variation from 18 to 40% between herds. In the herds, the wound lesions and the connective tissue formations accounted for 22% and 78% of all band-shaped tail lesions, respectively. Among 458 Holstein cows examined at an abattoir the prevalence of band-shaped tail lesions was 23%, i.e. similar to the prevalence within the herds. At the abattoir the share of band-shaped wound lesions was 67% and the band-shaped connective tissue formation 33%. Associations between the occurrence of band-shaped tail lesions and parity and lack of the tail tip were observed.
Journal Article
Mrs. Orville Isn't Trying to Steal Tips: An FLSA Story
A debate over tips and tipped employees, centered on a few provisions of the Fair Labor Standards Act (FLSA), has arisen among the circuits. Despite turning on only a few phrases in the FLSA, this judicial divide has massive implications for the restaurant and hospitality industries. One in ten working Americans is now employed in the restaurant industry, and the Internal Revenue Service (IRS) estimates that tips account for over $27 billion in wages each year. With such enormous stakes, this dispute has captured the attention of employee-rights advocates, restaurant and hospitality trade associations, and the Department of Labor (DOL).
Journal Article
An Insight Into the Role of Alpha-Fetoprotein (AFP) in the Development and Progression of Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the primary malignancy of hepatocytes and the second most common cause of cancer-related mortality across the globe. Despite significant advancements in screening, diagnosis, and treatment modalities for HCC, the mortality-to-incidence ratio remain unacceptably high. A recent study indicates that a minor population of HCCs are AFP negative or express the normal range of AFP levels. Although it is a gold standard and a more reliable biomarker in the advanced stage of HCC and poorly differentiated tumors, it does not serve as a suitable means for screening HCC. AFP plays a significant role in the development and progression of HCC and understanding its role is crucial. By examining the molecular mechanisms involved in AFP-mediated tumorigenesis, we can better understand HCC pathogenesis and identify potential therapeutic targets. This article details the role of alpha-fetoprotein (AFP) in the carcinogenic transformation of hepatocytes. The article also focuses on information about the structure, biosynthesis, and regulation of AFP at the gene level. Additionally, it discusses the immune evasion, metastasis, and control of gene expression that AFP mediates during HCC.
Graphical Abstract
Journal Article
A high-throughput microfluidic nanoimmunoassay for detecting anti–SARS-CoV-2 antibodies in serum or ultralow-volume blood samples
Novel technologies are needed to facilitate large-scale detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies in human blood samples. Such technologies are essential to support seroprevalence studies and vaccine clinical trials, and to monitor quality and duration of immunity. We developed a microfluidic nanoimmunoassay (NIA) for the detection of anti–SARS-CoV-2 IgG antibodies in 1,024 samples per device. The method achieved a specificity of 100% and a sensitivity of 98% based on the analysis of 289 human serum samples. To eliminate the need for venipuncture, we developed low-cost, ultralow-volume whole blood sampling methods based on two commercial devices and repurposed a blood glucose test strip. The glucose test strip permits the collection, shipment, and analysis of 0.6 μL of whole blood easily obtainable from a simple finger prick. The NIA platform achieves high throughput, high sensitivity, and specificity based on the analysis of 289 human serum samples, and negligible reagent consumption. We furthermore demonstrate the possibility to combine NIA with decentralized and simple approaches to blood sample collection. We expect this technology to be applicable to current and future SARS-CoV-2 related serological studies and to protein biomarker analysis in general.
Journal Article
Influence of circadian clocks on adaptive immunity and vaccination responses
The adaptive immune response is under circadian control, yet, why adaptive immune reactions continue to exhibit circadian changes over long periods of time is unknown. Using a combination of experimental and mathematical modeling approaches, we show here that dendritic cells migrate from the skin to the draining lymph node in a time-of-day-dependent manner, which provides an enhanced likelihood for functional interactions with T cells. Rhythmic expression of TNF in the draining lymph node enhances BMAL1-controlled ICAM-1 expression in high endothelial venules, resulting in lymphocyte infiltration and lymph node expansion. Lymph node cellularity continues to be different for weeks after the initial time-of-day-dependent challenge, which governs the immune response to vaccinations directed against Hepatitis A virus as well as SARS-CoV-2. In this work, we present a mechanistic understanding of the time-of-day dependent development and maintenance of an adaptive immune response, providing a strategy for using time-of-day to optimize vaccination regimes.
Circadian rhythms have been shown to influence immune responses, but it is unclear whether this influences responses to vaccines. Here the authors show that dendritic cells migrate in a circadian rhythm meaning that interactions with T cells are altered leading to differential vaccine responses.
Journal Article
Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs
Emerging SARS-CoV-2 variants raise questions about escape from previous immunity. As the population immunity to SARS-CoV-2 has become more complex due to prior infections with different variants, vaccinations or the combination of both, understanding the antigenic relationship between variants is needed. Here, we have assessed neutralizing capacity of 120 blood specimens from convalescent individuals infected with ancestral SARS-CoV-2, Alpha, Beta, Gamma or Delta, double vaccinated individuals and patients after breakthrough infections with Delta or Omicron-BA.1. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta and Omicron-BA.1) determined by plaque-reduction neutralization assay allowed us to map the antigenic relationship of SARS-CoV-2 variants. Highest neutralization titers were observed against the homologous variant. Antigenic cartography identified Zeta and Omicron-BA.1 as separate antigenic clusters. Substantial immune escape in vaccinated individuals was detected for Omicron-BA.1 but not Zeta. Combined infection/vaccination derived immunity results in less Omicron-BA.1 immune escape. Last, breakthrough infections with Omicron-BA.1 lead to broadly neutralizing sera.
Emerging SARS-CoV-2 variants raise concerns on protective immunity. Here the authors show that convalescent sera from people infected with Alpha, Beta, Gamma or Delta show a significant drop of Omicron-BA.1 neutralization and that vaccine-breakthrough infections with Omicron-BA.1 or Delta result in robust neutralization for both Delta and Omicron-BA.1.
Journal Article
Don't stress, it's under control: Neural correlates of stressor controllability in humans
•Non-painful aversive electric stimulation decreases vmPFC BOLD signal.•Adversity-related down-regulation of vmPFC is attenuated by controllability.•Attenuation of perceived helplessness is linked to greater vmPFC activation.•Results have implications for depression and stress resilience research.
Animal research has repeatedly shown that control is a key variable in the brain's stress response. Uncontrollable stress triggers a release of monoamines, impairing prefrontal functions while enhancing subcortical circuits. Conversely, control over an adverse event involves prefrontally mediated downregulation of monoamine nuclei and is considered protective. However, it remains unclear to what extent these findings translate to humans. During functional magnetic resonance imaging, we subjected participants to controllable and uncontrollable aversive but non-painful electric stimuli, as well as to a control condition without aversive stimulation. In each trial, a symbol signalled whether participants could terminate the stressor through correct performance in a button-matching task or whether the stressor would be randomly terminated, i.e., uncontrollable. Along with neural responses, we assessed participants’ accuracy, reaction times, and heart rate. To relate neural activations and subjective experience, we asked participants to rate perceived control, helplessness, and stress. Results were largely in line with our hypotheses. The vmPFC was generally deactivated by aversive stimulation, but this effect was attenuated when participants could terminate the stressor compared to when their responses had no effect. Furthermore, activation in stress-responsive regions, including the bilateral insula, was reduced during controllable trials. Under uncontrollable aversive stimulation, greater vmPFC recruitment was linked to reduced feelings of helplessness. An investigation of condition-dependant differences in vmPFC connectivity yielded no significant results. Our findings further corroborate animal research and emphasise the role of the vmPFC in controllability-dependant regulation of stress responses. Based on the results, we discuss future directions in the context of resilience research and mental health promotion.
Stressor-induced deactivation of the ventromedial prefrontal cortex is attenuated by instrumental control. Neural activation differences under controllable and uncontrollable aversive stimulation are linked to subjective experience. [Display omitted]
Journal Article