Exclusionary pricing in two-sided markets

This paper studies the incentives to engage in exclusionary pricing in the context of two-sided markets. Platforms are horizontally differentiated, and seek to attract users of two groups who single-home and enjoy indirect network externalities from the size of the opposite user group active on the same platform. The entrant incurs a fixed cost of entry, and the incumbent can commit to its prices before the entry decision is taken. The incumbent has thus the option to either accommodate entry, or to exclude entry and enjoy monopolistic profits, albeit under the constraint that its price must be low enough to not leave any room for an entrant to cover its fixed cost of entry. We find that, in the spirit of the literature on limit pricing, under certain circumstances even platforms find it profitable to exclude entrants if the fixed entry cost lies above a certain threshold. By studying the properties of the threshold, we show that the stronger the network externality, the lower the thresholds for which incumbent platforms find it profitable to exclude. We also find that entry deterrence is more likely to harm consumers the weaker are network externalities, and the more differentiated are the two platforms

Cell death pathology: Cross-talk with autophagy and its clinical implications

AbstractAutophagy is a self-digesting mechanism that cells adopt to respond to stressful stimuli. Morphologically, cells dying by autophagy show multiple cytoplasmic double-membraned vacuoles, and, if prolonged, autophagy can lead to cell death, "autophagic cell death". Thus, autophagy can act both as a temporary protective mechanism during a brief stressful episode and be a mode of cell death in its own right. In this mini-review we focus on recent knowledge concerning the connection between autophagy and programmed cell death, evaluating their possible implications for therapy in pathologies like cancer and neurodegeneration

Semi-Supervised Overlapping Community Finding based on Label Propagation with Pairwise Constraints

Algorithms for detecting communities in complex networks are generally unsupervised, relying solely on the structure of the network. However, these methods can often fail to uncover meaningful groupings that reflect the underlying communities in the data, particularly when those structures are highly overlapping. One way to improve the usefulness of these algorithms is by incorporating additional background information, which can be used as a source of constraints to direct the community detection process. In this work, we explore the potential of semi-supervised strategies to improve algorithms for finding overlapping communities in networks. Specifically, we propose a new method, based on label propagation, for finding communities using a limited number of pairwise constraints. Evaluations on synthetic and real-world datasets demonstrate the potential of this approach for uncovering meaningful community structures in cases where each node can potentially belong to more than one community.Comment: Fix table

The transcriptional transactivator Tat selectively regulates viral splicing

HIV-1 gene expression requires both viral and cellular factors to control and coordinate transcription. While the viral factor Tat is known for its transcriptional transactivator properties, we present evidence for an unexpected function of Tat in viral splicing regulation. We used a series of HIV-1 reporter minigenes to demonstrate that Tat’s role in splicing is dependent on the cellular co-transcriptional splicing activators Tat-SF1 and CA150. Surprisingly, we show that this Tat-mediated splicing function is independent from transcriptional activation. In the context of the full-length viral genome, this mechanism promotes an autoregulatory feedback that decreases expression of tat and favors expression of the env-specific mRNA. Our data demonstrate that Tat-mediated regulation of transcription and splicing can be uncoupled and suggest a mechanism for the involvement of specific transcriptional activators in splicing

The role of individual social responsibility and corporate social responsibility in the tax fraud war: a comparison between the priorities of Italian and Romanian consumers

Corporate social responsibility (CSR) and fiscal responsibility have become a hot topic of debate in recent years. Many studies have investigated CSR and tax avoidance; however, such studies have overlooked countries' tax cultures and fiscal responsibility from a historical perspective and have not addressed how these elements affect current tax avoidance practices. Using a questionnaire, that was administered to a sample of Italian and Romanian respondents, and inferential techniques (Mann–Whitney-test and correlation-test) the paper tries to understand the aspects that be useful in the future development and implementation of more robust fiscal ISR and CSR processes. Our results reveal similarities and differences between the relevance of certain aspects between countries, identifying tax culture as a distinctive element from a geographical point of view. Despite the considerable differences, we found a strong demand for greater transparency of the company with administrations and communities and desire for the development of initiatives to spread a responsible tax culture

TAp73 promotes anabolism

Metabolic adaptation has emerged as a hallmark of cancer and a promising therapeutic target, as rapidly proliferating cancer cells adapt their metabolism increasing nutrient uptake and reorganizing metabolic fluxes to support biosynthesis. The transcription factor p73 belongs to the p53-family and regulates tumorigenesis via its two N-terminal isoforms, with (TAp73) or without (ΔNp73) a transactivation domain. TAp73 acts as tumor suppressor, at least partially through induction of cell cycle arrest and apoptosis and through regulation of genomic stability. Here, we sought to investigate whether TAp73 also affects metabolic profiling of cancer cells. Using high throughput metabolomics, we unveil a thorough and unexpected role for TAp73 in promoting Warburg effect and cellular metabolism. TAp73-expressing cells show increased rate of glycolysis, higher amino acid uptake and increased levels and biosynthesis of acetyl-CoA. Moreover, we report an extensive TAp73-mediated upregulation of several anabolic pathways including polyamine and synthesis of membrane phospholipids. TAp73 expression also increases cellular methyl-donor S-adenosylmethionine (SAM), possibly influencing methylation and epigenetics, and promotes arginine metabolism, suggestive of a role in extracellular matrix (ECM) modeling. In summary, our data indicate that TAp73 regulates multiple metabolic pathways that impinge on numerous cellular functions, but that, overall, converge to sustain cell growth and proliferation

The C terminus of p73 is essential for hippocampal development

The p53 family member p73 has a complex gene structure, including alternative promoters and alternative splicing of the 3′ UTR. This results in a complex range of isoforms whose biological relevance largely remains to be determined. By deleting exon 13 (which encodes a sterile α motif) from the Trp73 gene, we selectively engineered mice to replace the most abundantly expressed C-terminal isoform, p73α, with a shorter product of alternative splicing, p73β. These mice (Trp73Δ13/Δ13) display severe neurodevelopmental defects with significant functional and morphological abnormalities. Replacement of p73α with p73β results in the depletion of Cajal–Retzius (CR) cells in embryonic stages, thus depriving the developing hippocampus of the pool of neurons necessary for correct hippocampal architecture. Consequently, Trp73Δ13/Δ13 mice display severe hippocampal dysgenesis, reduced synaptic functionality and impaired learning and memory capabilities. Our data shed light on the relevance of p73 alternative splicing and show that the full-length C terminus of p73 is essential for hippocampal development

TAp73 contributes to the oxidative stress response by regulating protein synthesis.

TAp73 is a transcription factor that plays key roles in brain development, aging, and cancer. At the cellular level, TAp73 is a critical homeostasis-maintaining factor, particularly following oxidative stress. Although major studies focused on TAp73 transcriptional activities have indicated a contribution of TAp73 to cellular metabolism, the mechanisms underlying its role in redox homeostasis have not been completely elucidated. Here we show that TAp73 contributes to the oxidative stress response by participating in the control of protein synthesis. Regulation of mRNA translation occupies a central position in cellular homeostasis during the stress response, often by reducing global rates of protein synthesis and promoting translation of specific mRNAs. TAp73 depletion results in aberrant ribosomal RNA (rRNA) processing and impaired protein synthesis. In particular, polysomal profiles show that TAp73 promotes the integration of mRNAs that encode rRNA-processing factors in polysomes, supporting their translation. Concurrently, TAp73 depletion causes increased sensitivity to oxidative stress that correlates with reduced ATP levels, hyperactivation of AMPK, and translational defects. TAp73 is important for maintaining active translation of mitochondrial transcripts in response to oxidative stress, thus promoting mitochondrial activity. Our results indicate that TAp73 contributes to redox homeostasis by affecting the translational machinery, facilitating the translation of specific mitochondrial transcripts. This study identifies a mechanism by which TAp73 contributes to the oxidative stress response and describes a completely unexpected role for TAp73 in regulating protein synthesis

BAG3 protein regulates stress- induced apoptosis in normal and neoplastic leukocytes

Co-chaperone proteins that share the Bcl-2-associated athanogene (BAG) domain are characterized by their interaction with a variety of partners, such as heat shock proteins (Hsp), steroid hormone receptors, Bcl-2, Raf-1 and others, involved in regulating protein folding and a number of cellular processes, including proliferation and apoptosis. Among BAG family members there is BAG3, also known as CAIR-1 or Bis. BAG3 forms a complex with Hsp70,1,2,4,6 a protein able to modulate apoptosis by interfering with cytochrome c release, apoptosome assembly and other events in the death process. In addition, BAG3 polypeptide binds to phospholipase C-g (PLC-g)4 or Bcl-2 protein.3,5 Due to such interaction with more than one apoptosis-modulating factor, BAG3 can participate in apoptosis regulation. Indeed, its hyperexpression can decrease apoptosis induced via Bax or Fas in the human epithelial cell line HeLa3 or by IL-3 deprivation in the murine hematopoietic cell line 32D.5 Furthermore, we recently showed that BAG3 downmodulation enhances the apoptotic response to chemotherapy in human primary B chronic lymphocytic leukemia cell