NF-κB and its role in checkpoint control

Nuclear factor-κB (NF-κB) has been described as one of the most important molecules linking inflammation to cancer. More recently, it has become clear that NF-κB is also involved in the regulation of immune checkpoint expression. Therapeutic approaches targeting immune checkpoint molecules, enabling the immune system to initiate immune responses against tumor cells, constitute a key breakthrough in cancer treatment. This review discusses recent evidence for an association of NF-κB and immune checkpoint expression and examines the therapeutic potential of inhibitors targeting either NF-κB directly or molecules involved in NF-κB regulation in combination with immune checkpoint blockade

A Fast Counting Method for 6-motifs with Low Connectivity

A $k$-motif (or graphlet) is a subgraph on $k$ nodes in a graph or network. Counting of motifs in complex networks has been a well-studied problem in network analysis of various real-word graphs arising from the study of social networks and bioinformatics. In particular, the triangle counting problem has received much attention due to its significance in understanding the behavior of social networks. Similarly, subgraphs with more than 3 nodes have received much attention recently. While there have been successful methods developed on this problem, most of the existing algorithms are not scalable to large networks with millions of nodes and edges. The main contribution of this paper is a preliminary study that genaralizes the exact counting algorithm provided by Pinar, Seshadhri and Vishal to a collection of 6-motifs. This method uses the counts of motifs with smaller size to obtain the counts of 6-motifs with low connecivity, that is, containing a cut-vertex or a cut-edge. Therefore, it circumvents the combinatorial explosion that naturally arises when counting subgraphs in large networks

Dataset of characteristic remanent magnetization and magnetic properties of early Pliocene sediments from IODP Site U1467 (Maldives platform)

This data article describes data of magnetic stratigraphy and anisotropy of isothermal remanent magnetization (AIRM) from "Magnetic properties of early Pliocene sediments from IODP Site U1467 (Maldives platform) reveal changes in the monsoon system" [1]. Acquisition of isothermal magnetization on pilot samples and anisotropy of isothermal remanent magnetization are reported as raw data; magnetostratigraphic data are reported as characteristic magnetization (ChRM).info:eu-repo/semantics/publishedVersio

On Structural Parameterizations of the Bounded-Degree Vertex Deletion Problem

We study the parameterized complexity of the Bounded-Degree Vertex Deletion problem (BDD), where the aim is to find a maximum induced subgraph whose maximum degree is below a given degree bound. Our focus lies on parameters that measure the structural properties of the input instance. We first show that the problem is W[1]-hard parameterized by a wide range of fairly restrictive structural parameters such as the feedback vertex set number, pathwidth, treedepth, and even the size of a minimum vertex deletion set into graphs of pathwidth and treedepth at most three. We thereby resolve an open question stated in Betzler, Bredereck, Niedermeier and Uhlmann (2012) concerning the complexity of BDD parameterized by the feedback vertex set number. On the positive side, we obtain fixed-parameter algorithms for the problem with respect to the decompositional parameter treecut width and a novel problem-specific parameter called the core fracture number

BTK isoforms p80 and p65 are expressed in head and neck squamous cell carcinoma (HNSCC) and involved in tumor progression

Here, we describe the expression of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients

A Duration-Dependent Interaction Between High-Intensity Light and Unrestricted Vision in the Drive for Myopia Control

Purpose: To evaluate the duration-dependent and synergetic impact of high-intensity light (HL) and unrestricted vision (UnV) on lens-induced myopia (LIM) development in chickens. Methods: Myopia was induced in one eye in chicks (10 groups, n = 126) from day 1 posthatching (D1) until day 8 (D8) using –10 diopter (D) lenses. Fellow eyes remained uncovered as controls. Nine groups were exposed daily to 2, 4, or 6 hours of HL (15,000 lux), UnV (removal of –10 D lens), or both (HL + UnV). One group served as the LIM group without any interventions. Ocular axial length (AL), refractive error, and choroidal thickness were measured on D1, D4, and D8. Outcome measures are expressed as interocular difference (IOD = experimental eye – control eye) ± SEM. Results: By D8, LIM increased AL (0.36 ± 0.04 mm), myopic refraction (−9.02 ± 0.37 D), and choroidal thinning (−90.27 ± 16.44 µm) in the LIM group (all, P < 0.001). Compared to the LIM group, exposure to 2, 4, or 6 hours of HL, UnV, or HL + UnV reduced myopic refraction in a duration-dependent manner, with UnV being more effective than HL (P < 0.05). Only 6 hours of HL + UnV (not 2 or 4 hours) prevented LIM and was more effective than UnV (P = 0.004) or HL (P < 0.001) in reducing myopic refraction and more effective than HL (P < 0.001) in reducing axial elongation. Conclusions: Daily exposure to 2, 4, or 6 hours of HL, UnV, or HL + UnV reduced lens-induced myopic refraction in a duration-dependent manner in chickens. Only 6 hours of HL + UnV completely stopped LIM development. The synergetic effect of HL and UnV is dependent on the duration of the interventions

The abrupt onset of the modern South Asian Monsoon winds

The South Asian Monson (SAM) is one of the most intense climatic elements yet its initiation and variations are not well established. Dating the deposits of SAM wind-driven currents in IODP cores from the Maldives yields an age of 12. 9 Ma indicating an abrupt SAM onset, over a short period of 300 kyrs. This coincided with the Indian Ocean Oxygen Minimum Zone expansion as revealed by geochemical tracers and the onset of upwelling reflected by the sediment's content of particulate organic matter. A weaker 'proto-monsoon' existed between 12.9 and 25 Ma, as mirrored by the sedimentary signature of dust influx. Abrupt SAM initiation favors a strong influence of climate in addition to the tectonic control, and we propose that the post Miocene Climate Optimum cooling, together with increased continentalization and establishment of the bipolar ocean circulation, i.e. the beginning of the modern world, shifted the monsoon over a threshold towards the modern system

Corrigendum to “Carbonate delta drift: A new sediment drift type” [Mar. Geol. 401 (2018) 98–111]

The authors regret the mistake in the drawing of the delta drift architecture in figure 11. The authors would like to apologise for any inconvenience caused. [Figure presented

Modern rhodolith-dominated carbonates at Punta Chivato, Mexico

Rhodolith-dominated carbonate environments, characterized by high abundances of free-living coralline algae, have been described globally from a wide range of Recent and fossil shallow marine settings. In the present-day warm-temperate Gulf of California, Mexico, rhodolith-dominated systems are important contributors to carbonate production. One of the most prolific rhodolith factories is located on the Punta Chivato shelf, in the central Gulf of California, where due to a lack of input of terrigenous material from the arid hinterland, carbonate content averages 79%. Punta Chivato rhodoliths thrive above the shallow euphotic zone under normal saline, warm-temperate and meso- to eutrophic conditions. A detailed sedimentologic study combined with acoustic seafloor mapping indicates the presence of extensive rhodolith-dominated facies at subtidal water depth covering an area of \u3e17 km2. Additional facies, surrounding the rhodolith-dominated facies include a fine-grained molluscan, a transitional bivalve-rhodolith and a bivalve facies. While the Punta Chivato shelf yields average abundances of 38% rhodolith-derived coralline algal components in the gravel-sized sediment fraction, the rhodolith facies itself is characterized by more than 60% coralline algal components. Other important carbonate producers at Punta Chivato include bivalves (35%), bryozoa (11%) and gastropods (8%). The present study shows that acoustic sediment mapping yields highly resolved continuous coverage of the seafloor and can distinguish modern rhodolith facies from surrounding sediment. This has important implications for quantifying rhodolith-dominated settings globally, as well as for ecological and conservation studies. © Publications Scientifiques du Muséum national d\u27Histoire naturelle, Paris