Stress pathways monitor intracellular systems and deploy a range of regulatory mechanisms in response to stress. One of the best-characterized pathways, the UPR (unfolded protein response), is an ...intracellular signal transduction pathway that monitors ER (endoplasmic reticulum) homoeostasis. Its activation is required to alleviate the effects of ER stress and is highly conserved from yeast to human. Although metazoans have three UPR outputs, yeast cells rely exclusively on the Ire1 (inositol-requiring enzyme-1) pathway, which is conserved in all Eukaryotes. In general, the UPR program activates hundreds of genes to alleviate ER stress but it can lead to apoptosis if the system fails to restore homoeostasis. In this review, we summarize the major advances in understanding the response to ER stress in Sc (Saccharomyces cerevisiae), Sp (Schizosaccharomyces pombe) and humans. The contribution of solved protein structures to a better understanding of the UPR pathway is discussed. Finally, we cover the interplay of ER stress in the development of diseases.
Interleukin (IL)-11 evolved as part of the innate immune response. In the human lung, IL-11 upregulation has been associated with viral infections and a range of fibroinflammatory diseases, including ...idiopathic pulmonary fibrosis. Transforming growth factor-beta (TGFβ) and other disease factors can initiate an autocrine loop of IL-11 signaling in pulmonary fibroblasts, which, in a largely ERK-dependent manner, triggers the translation of profibrotic proteins. Lung epithelial cells also express the IL-11 receptor and transition into a mesenchymal-like state in response to IL-11 exposure. In mice, therapeutic targeting of IL-11 with antibodies can arrest and reverse bleomycin-induced pulmonary fibrosis and inflammation. Intriguingly, fibroblast-specific blockade of IL-11 signaling has anti-inflammatory effects, which suggests that lung inflammation is sustained, in part, through IL-11 activity in the stroma. Proinflammatory fibroblasts and their interaction with the damaged epithelium may represent an important but overlooked driver of lung disease. Initially thought of as a protective cytokine, IL-11 is now increasingly recognized as an important determinant of lung fibrosis, inflammation, and epithelial dysfunction.
Tuberculosis (TB) remains a global health threat, with over a third of the world population suffering from the disease, and 1.5 million deaths due to the disease in 2013 alone. Despite significant ...advances in TB detection strategies in recent years, a bigger push toward detecting TB in the shortest and easiest way possible at the point-of-care (POC) is still in demand. To this end, we have designed a simple yet rapid and sensitive bioassay that detects Mtb DNA electrochemically using colloidal gold nanoparticles. This assay couples rapid isothermal amplification of target DNA that is specific to Mtb with gold nanoparticle electrochemistry on disposable screen printed carbon electrodes. The assay is capable of detecting a positive differential pulse voltammetry (DPV) response from as low as 1 CFU of Mtb bacilli DNA input material, having shown its exquisite sensitivity over a conventional gel based readout. The translation of our assay onto a portable potentiostat was also demonstrated, with promising results. We believe that our assay has significant potential for translation into broader bioassay applications or development as a POC diagnostic tool.
SignificanceThe western Pacific subtropical high (WPSH) channels moisture from the tropics that underpins the East Asian summer climate. Interannual variability of the WPSH dominates climate extremes ...in the densely populated countries of East Asia. In 2020, an anomalously strong WPSH led to catastrophic floods with hundreds of deaths, 28,000 homes destroyed, and tens of billions in economic damage in China alone. How the frequency of such strong WPSH events will change is of great societal concern. Our finding of an increase in future WPSH variability, translating into an increased frequency of climate extreme as seen in the 2020 episode, highlights the increased risks for the billions of people in the densely populated East Asia with profound socioeconomic consequences.
In this paper, the channel coding performance with finite-alphabet inputs and finite blocklength in a two-user downlink non-orthogonal-multiple-access (NOMA) system is characterized from an ...information-theoretic perspective, and optimized with proper power allocation and constellation design. While previous works in NOMA were mainly focused on either infinite blocklength performance or finite blocklength performance with Gaussian inputs, we obtain the information-theoretic achievable rates accurate up to second-order as a function of the blocklength for both NOMA users employing finite-alphabet inputs subject to the average total power constraint. Taking advantage of the theoretical results, we formulate the rate and error-rate performance optimization problems in the finite blocklength regime for finite-alphabet inputs, from which the optimal power allocation and constellation-rotation can be derived. Furthermore, polar codes and LDPC are employed to demonstrate how close their performances are from the second-order achievable bound when the blocklength is short. Our results are important in machine-type or IoT communications where lightweight modulations and short blocklength are more relevant compared with traditional Gaussian-inputs assumption.
The 2019 positive Indian Ocean Dipole (IOD) was the strongest event since the 1960s which developed independently without coinciding El Niño. The dynamics is not fully understood. Here we show that ...in March–May, westward propagating oceanic Rossby waves, a remnant consequence of the weak 2018 Pacific warm condition, led to anomalous sea surface temperature warming in the southwest tropical Indian Ocean (TIO), inducing deep convection and anomalous easterly winds along the equator, which triggered the initial cooling in the east. In June–August, the easterly wind anomalies continued to evolve through ocean‐atmosphere coupling involving Bjerknes feedback and equatorial nonlinear ocean advection, until its maturity in September–November. This study clarifies the contribution of oceanic Rossby waves in the south TIO in different dynamic settings and reveals a new triggering mechanism for extreme IOD events that will help to understand IOD diversity.
Plain Language Summary
The Indian Ocean Dipole (IOD) is an ocean‐atmosphere coupled climatic phenomenon which can cause severe social and economic losses in the surrounding regions such as drought in the Maritime Continent/Australia and flooding in East Africa. The IOD features a see‐saw structure accompanied by an anomalous sea surface temperature gradient, winds, and oceanic adjustments. The El Niño–Southern Oscillation in the Pacific is an important trigger to a strong IOD event. However, an extreme positive IOD event occurred in 2019 without a concurrent or ensuing El Niño. We show that the thermocline warming associated with anomalous ocean downwelling in the southwest tropical Indian Ocean triggered atmospheric convection, inducing anomalous easterly winds along the equator and hence, positive feedbacks associated with an IOD event. This study may help to understand the evolution of extreme IOD and improve IOD predictability.
Key Points
The oceanic downwelling Rossby waves in the south tropical Indian Ocean is key to the 2019 extreme positive Indian Ocean Dipole (IOD)
The Rossby waves induced thermocline warming, triggering wind‐evaporation‐SST feedback thus anomalous easterly winds along the equator
The easterly wind anomalies further triggered the Bjerknes feedback and other positive feedbacks and established an extreme IOD
Compared with traditional low-density parity-check (LDPC) decoding algorithms, the current model-driven deep learning (DL)-based LDPC decoding algorithms face the disadvantage of high computational ...complexity. Based on the Neural Normalized Min-Sum (NNMS) algorithm, we propose a low-complexity model-driven DL-based LDPC decoding algorithm using Tensor-Train (TT) decomposition and syndrome loss function, called TT-NNMS+ algorithm. Our experiments show that the proposed TT-NNMS+ algorithm is more competitive than the NNMS algorithm in terms of bit error rate (BER) performance, memory requirement and computational complexity.
Rainfall anomalies over southern China are found to be asymmetricly influenced by the Indian Ocean Dipole (IOD), with a far stronger influence from positive IOD (pIOD) events. A greater convection ...anomaly and an equivalent-barotropic Rossby wave train response occurs during pIOD events than during negative IOD (nIOD) events. Over the Bay of Bengal (BOB) and South China Sea (SCS), an associated low-level anomalous anticyclone strengthens the southwesterlies during boreal fall (September, October and November, SON), when a pIOD matures. The increased moisture flux gives rise to the anomalously high rainfall over southern China. During its developing phase (boreal summer, June, July, and August, JJA), the influence of a pIOD event on the contemporaneous rainfall over southern China is weak, but a JJA pIOD index is highly correlated with fall rainfall. Therefore, this index can serve as a potential predictor for variations of boreal fall rainfall over southern China.
El Niño and La Niña, collectively referred to as the El Niño-Southern Oscillation (ENSO), are not only highly consequential
but also strongly nonlinear
. For example, the maximum warm anomalies of El ...Niño, which occur in the equatorial eastern Pacific Ocean, are larger than the maximum cold anomalies of La Niña, which are centred in the equatorial central Pacific Ocean
. The associated atmospheric nonlinear thermal damping cools the equatorial Pacific during El Niño but warms it during La Niña
. Under greenhouse warming, climate models project an increase in the frequency of strong El Niño and La Niña events, but the change differs vastly across models
, which is partially attributed to internal variability
. Here we show that like a butterfly effect
, an infinitesimal random perturbation to identical initial conditions induces vastly different initial ENSO variability, which systematically affects its response to greenhouse warming a century later. In experiments with higher initial variability, a greater cumulative oceanic heat loss from ENSO thermal damping reduces stratification of the upper equatorial Pacific Ocean, leading to a smaller increase in ENSO variability under subsquent greenhouse warming. This self-modulating mechanism operates in two large ensembles generated using two different models, each commencing from identical initial conditions but with a butterfly perturbation
; it also operates in a large ensemble generated with another model commencing from different initial conditions
and across climate models participating in the Coupled Model Intercomparison Project
. Thus, if the greenhouse-warming-induced increase in ENSO variability
is initially suppressed by internal variability, future ENSO variability is likely to be enhanced, and vice versa. This self-modulation linking ENSO variability across time presents a different perspective for understanding the dynamics of ENSO variability on multiple timescales in a changing climate.
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