IEEE / Institute of Electrical and Electronics Engineers Incorporated

IEEE Computer Society

IEEE Computer Society

IEEE / Institute of Electrical and Electronics Engineers Incorporated

IEEE / Institute of Electrical and Electronics Engineers Incorporated

National Bureau of Economic Research

IEEE Computer Society

IEEE / Institute of Electrical and Electronics Engineers Incorporated

IEEE / Institute of Electrical and Electronics Engineers Incorporated

IEEE / Institute of Electrical and Electronics Engineers Incorporated

IEEE / Institute of Electrical and Electronics Engineers Incorporated

IEEE / Institute of Electrical and Electronics Engineers Incorporated

IEEE / Institute of Electrical and Electronics Engineers Incorporated

IEEE / Institute of Electrical and Electronics Engineers Incorporated

IEEE / Institute of Electrical and Electronics Engineers Incorporated

Kremlin spokesman Dmitry Pesko said it was hard to predict "to what extent he's going to stick to statements that he made on the campaign trail"

"There is certain progress," Foreign Minister Gideon Saar said after being asked about a possible ceasefire.

Dave's about to be eclipsed, the state of TypeScript in 2024, signals stage zero proposal, corrections on accessibility in frameworks (thanks!), web apps for better collaborative writing, getting productivity sniped, the problem with email may be you, indieweb follow up, and ultimate guitar tab apps.

It offers two pathways for countries and companies to trade carbon offsets, supporting the achievement of emission reduction targets set in their climate action plans, or nationally determined contributions

Such a market would allow countries to trade carbon credits among themselves

India’s services PMI rebounds to 58.5 in October, driven by strong output, new business, and job creation, signaling economic growth

Stretchable strain and pressure sensor might one day guide rehabilitation

Sensex, Nifty, Share Prices LIVE: Gift Nifty indicates a likely 100-point gap-down opening for Nifty at 23,870 on Wednesday as global markets remain weak. Analysts cite concerns over an earnings slowdown and persistently high inflation; Jefferies India downgraded full-year earnings for 63% of the 121 large companies it covers due to economic slowing. India’s retail inflation surged to a 14-month high of 6.21% in October, with steep rises in food and metal prices potentially influencing the RBI’s December policy stance. A continued hold on rates seems likely, but analysts at AngelOne note a shallower rate-cut cycle ahead for India, mirroring the US trend. Options data signals resistance around 24,500 due to heavy call writing and support near 23,500, with a bearish put-call ratio drop to 0.52. India VIX rose to 14.60 (+2.40%), suggesting caution; however, lower volatility generally supports bullish sentiment, according to SAMCO’s Dhupesh Dhameja.

'It (the decision to pick Nitish ahead of Shardul) is also about moving forward and I feel that this is the best set of players that we have selected to do the job for the country.'

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.

Protease-activated receptor 2 (PAR-2) is activated by secreted proteases from immune cells or fungi. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. We hypothesized that epithelial remodeling during diseases characterized by cilial loss and squamous metaplasia may alter PAR-2 polarization. Here, using a fluorescent arrestin assay, we confirmed that the common fungal airway pathogen Aspergillus fumigatus activates heterologously-expressed PAR-2. Endogenous PAR-2 activation in submerged airway RPMI 2650 or NCI–H520 squamous cells increased intracellular calcium levels and granulocyte macrophage–colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-6 secretion. RPMI 2650 cells cultured at an air–liquid interface (ALI) responded to apically or basolaterally applied PAR-2 agonists. However, well-differentiated primary nasal epithelial ALIs responded only to basolateral PAR-2 stimulation, indicated by calcium elevation, increased cilia beat frequency, and increased fluid and cytokine secretion. We exposed primary cells to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency, at concentrations and times that altered epithelial morphology without causing breakdown of the epithelial barrier to model early disease states. These altered primary cultures responded to both apical and basolateral PAR-2 stimulation. Imaging nasal polyps and control middle turbinate explants, we found that nasal polyps, but not turbinates, exhibit apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyps and turbinates maintained basolateral PAR-2 polarization, suggesting that the calcium responses originated from nonciliated cells. Altered PAR-2 polarization in disease-remodeled epithelia may enhance apical responses and increase sensitivity to inhaled proteases.