Impact of the clinically approved BTK inhibitors on the conformation of full-length BTK and analysis of the development of BTK resistance mutations in chronic lymphocytic leukemia.

Inhibition of Bruton's tyrosine kinase (BTK) has proven to be highly effective in the treatment of B-cell malignancies such as chronic lymphocytic leukemia (CLL), autoimmune disorders, and multiple sclerosis. Since the approval of the first BTK inhibitor (BTKi), Ibrutinib, several other inhibitors including Acalabrutinib, Zanubrutinib, Tirabrutinib, and Pirtobrutinib have been clinically approved. All are covalent active site inhibitors, with the exception of the reversible active site inhibitor Pirtobrutinib.

Investigation on Tattoo Ink (Hexadecachlorinate Copper Phthalocyanine) Removal: Novel Chemical and Biological Approach.

Tattoos have been a ubiquitous phenomenon throughout history. Now, the demand for tattoo removal for aesthetic or practical reasons is growing rapidly. This study outlines the results of field investigations into the chemical and biological removal of tattoo inks (Hexadecachlorinate copper phthalocyanine-CClCuN-CAS no° 1328-53-6).

Painful sexual intercourse, quality of life and sexual function in patients with endometriosis: not just deep dyspareunia.

Purpose: To evaluate the prevalence of deep and superficial dyspareunia in women with diagnosis of endometriosis. Secondly, to assess the temporal relation between deep and superficial dyspareunia in women reporting both symptoms (concomitant dyspareunia) and the impact on quality of life (QoL) and sexual function.

Methods: This is a cross-sectional cohort study that included fertile women with diagnosis of endometriosis.

Allosteric regulation of kinase activity.

The articles in this special issue highlight how modern cellular, biochemical, biophysical and computational techniques are allowing deeper and more detailed studies of allosteric kinase regulation.

Cancer incidence in immigrants by geographical area of origin: data from the Veneto Tumour Registry, Northeastern Italy.

Objective: We investigated whether there are differences in cancer incidence by geographical area of origin in North-eastern Italy.

Methods: We selected all incident cases recorded in the Veneto Tumour Registry in the period 2015-2019. Subjects were classified, based on the country of birth, in six geographical areas of origin (Italy, Highly Developed Countries-HDC, Eastern Europe, Asia, Africa, South-central America).

Distributed Dynamic Event-Triggered Control for Voltage Recovery in Islanded Microgrids by Using Artificial Delays.

This article tackles secondary voltage recovery problem in islanded microgrids with the aim of reducing communication frequency among distributed generation (DG) units, while maintaining desired performance and saving communication network workload. To pursue this objective, a distributed proportional-integral-derivative controller is first introduced, whose sampled-data implementation is enabled by leveraging the finite-difference approximation for the derivative action, which leads to a distributed proportional-integral-retarded (PIR) controller with a small enough sampling period . Then, the resulting fully distributed PIR control law is combined with a dynamic event-triggered mechanism (DETM), which embeds Zeno-freeness property and avoids the requirement of continuous transmission in triggering process.

Conformational heterogeneity of the BTK PHTH domain drives multiple regulatory states.

Full-length Bruton's tyrosine kinase (BTK) has been refractory to structural analysis. The nearest full-length structure of BTK to date consists of the autoinhibited SH3-SH2-kinase core. Precisely how the BTK N-terminal domains (the Pleckstrin homology/Tec homology [PHTH] domain and proline-rich regions [PRR] contain linker) contribute to BTK regulation remains unclear.

Screening and Characterization of Allosteric Small Molecules Targeting Bruton's Tyrosine Kinase.

Bruton's Tyrosine Kinase (BTK) is a nonreceptor tyrosine kinase that belongs to the TEC family. Mutations in the gene cause X-linked agammaglobulinemia (XLA) leading to an arrest in B-cell development. BTK is also a drug target for B-cell lymphomas that rely on an intact B-cell receptor signaling cascade for survival.

Conformational heterogeneity of the BTK PHTH domain drives multiple regulatory states.

Full-length BTK has been refractory to structural analysis. The nearest full-length structure of BTK to date consists of the autoinhibited SH3-SH2-kinase core. Precisely how the BTK N-terminal domains (the Pleckstrin homology/Tec homology (PHTH) domain and proline-rich regions (PRR) contain linker) contribute to BTK regulation remains unclear.

Structure of BTK kinase domain with the second-generation inhibitors acalabrutinib and tirabrutinib.

Bruton's tyrosine kinase (BTK) is the target of the therapeutic agent, Ibrutinib, that treats chronic lymphocyte leukemia (CLL), mantle cell lymphoma (MCL) and other B cell malignancies. Ibrutinib is a first in class, covalent BTK inhibitor that limits B-cell survival and proliferation. Designing new inhibitors of BTK has been an important objective for advancing development of improved therapeutic agents against cancer and autoimmune disorders.

Weather, sex and body condition affect post-fledging migration behaviour of the greater flamingo Phoenicopterus roseus.

Background: Understanding which intrinsic and extrinsic factors dictate decision-making processes such as leaving the natal area or not (migratory vs resident strategy), departure time, and non-breeding destination are key-issues in movement ecology. This is particularly relevant for a partially migratory meta-population in which only some individuals migrate.

Methods: We investigated these decision making-processes for 40 juvenile greater flamingos Phoenicopterus roseus fledged in three Mediterranean colonies and equipped with GPS-GSM devices.

Modelling the timing of migration of a partial migrant bird using ringing and observation data: a case study with the Song Thrush in Italy.

Background: The study of the timing of migration is fundamental to the understanding of the ecology of many bird species and their response to climate change, and it has important conservation and management implications e.g., for assessing the hunting seasons according to the EU Directive 2009/147/EC (Birds Directive).

Cytotoxicity of cleaning agents for ocular prostheses.

Background: Polymethylmethacrylate (PMMA) is the most used material for the manufacturing of eye prostheses.

Objectives: To investigate the cytotoxicity of different cleaning agents for ocular prostheses on human conjunctival cells.

Material And Methods: Six groups of specimens were created (saline, soap, 4% chlorhexidine, hydrogen peroxide, 1% triclosan, and citronella oil).

Management of nipple adenomas during pregnancy: a case report.

Background: Nipple adenoma is a very uncommon, benign neoplasm that involves the nipple. A palpable mass of the nipple associated with nipple discharge and erosion or ulceration is the common clinical presentation. Generally, complete surgical excision of the nipple is the main treatment, alternative therapeutic methods such as Mohs micrographic surgery, nipple splitting enucleation, and cryotherapy can be considered.

Damaging and protective interactions of lichens and biofilms on ceramic dolia and sculptures of the International Museum of Ceramics, Faenza, Italy.

Although ceramic objects are an important part of the worldwide cultural heritage, few investigations on the effects of lithobiontic growth on their outdoor conservation are available in the literature. Many aspects of the interaction between lithobionts and stones are still unknown or strongly debated, as in the case of equilibria between biodeterioration and bioprotection. This paper describes research on the colonization by lithobionts on outdoor ceramic Roman dolia and contemporary sculptures of the International Museum of Ceramics, Faenza (Italy).

Antibiofilm effect of cleaning agents for ocular prostheses.

Introduction: This study aimed to evaluate the antibiofilm effect of different agents (neutral soap, 4% chlorhexidine, Efferdent effervescent tablets, 1% triclosan, and citronella essential oil) used for ocular prosthesis cleaning.

Material And Methods: Biofilms of S. aureus and S.

The HIV-1 protein Nef activates the Tec family kinase Btk by stabilizing an intermolecular SH3-SH2 domain interaction.

The Nef protein produced by the viruses HIV-1 and SIV drives efficient viral replication partially by inducing constitutive activation of host cell tyrosine kinases, including members of the Src and Tec families. Here, we uncovered the mechanism by which both HIV-1 and SIV Nef enhanced the activity of the Tec family kinase Btk in vitro and in cells. A Nef mutant that could not bind to the SH3 domain of Src family kinases activated Btk to the same extent as did wild-type Nef, demonstrating that Nef activated Src and Tec family kinases by distinct mechanisms.

Ewing's Sarcoma of the Breast in a Young Woman: A Case Report and Review of the Literature.

Ewing's Sarcoma Family Tumors (ESFT) include classic Ewing's sarcoma of bone, extra-skeletal Ewing's sarcoma (EES), malignant small cell tumor of the chest wall (Askin tumor), and soft tissue-based Peripheral Primitive Neuroectodermal tumors (pPNET). The t(11;22)(q24;q12) translocation is associated with 85% of tumors and leads to EWS-FLI-1 (Ewing's Sarcoma-Friend Leukemia Integration-1) formation. This is a potent transforming gene that encodes a chimeric protein that plays a role in the genesis of Ewing's Sarcoma and Primitive Neuroectodermal Tumors.

Biodeterioration of carbographic ribbon: Isolation, identification of causal agents and forensic implications.

Unlabelled: This study is part of a comprehensive investigation that was performed in regard to a case of alterations on a carbographic ribbon used in a typewriter that was found and seized by inner security operations of the Arma dei Carabinieri, Italy. Thirty-six coded scripts possessing potentially and criminally liable content were present on the tape; however, only the 6th and 7th scripts exhibited alterations of an uncertain nature. The study included sampling that was performed under sterile conditions of a large surface area of carbographic ribbons.

Lead ammunition residues in a hunted Australian grassland bird, the stubble quail (Coturnix pectoralis): Implications for human and wildlife health.

Scavenging and predatory wildlife can ingest lead (Pb) from lead-based ammunition and become poisoned when feeding on shot game animals. Humans can similarly be exposed to ammunition-derived lead when consuming wild-shot game animals. Studies have assessed the degree of lead contamination in the carcasses of game animals but this scrutiny has not so far extended to Australia.

Conformational switches that control the TEC kinase - PLCγ signaling axis.

Cell surface receptors such as the T-cell receptor (TCR) and B-cell receptor (BCR) engage with external stimuli to transmit information into the cell and initiate a cascade of signaling events that lead to gene expression that drives the immune response. At the heart of controlling T- and B-cell cell signaling, phospholipase Cγ hydrolyzes membrane associated PIP, leading to generation of the second messengers IP and DAG. These small molecules trigger mobilization of intracellular Ca and promote transcription factor transport into the nucleus launching the adaptive immune response.