What Happens When Undergraduate Biology Students Meet with Professional Scientists to Discuss Research? An Exploratory Investigation into Scientific Discourse, Motivation, and Sense of Belonging.

Engagement in scientific discourse is an essential part of becoming a scientist. In this exploratory study, we aim to examine the scientific discourse (and resulting benefits) between undergraduate biology students and professional scientists. We developed a novel method for engaging in scientific discourse, grounded in the theory of legitimate peripheral participation, where undergraduate biology students participate in communities of practice within their own departments.

ETx-22, a Novel Nectin-4-Directed Antibody-Drug Conjugate, Demonstrates Safety and Potent Antitumor Activity in Low-Nectin-4-Expressing Tumors.

ETx-22, a novel ADC combining a tumor nectin-4-specific antibody and an innovative linker to exatecan, demonstrates significant and durable responses in low-target-expressing tumor models that are resistant to MMAE-based EV and has a better toxicity profile. This new ADC has the potential to benefit additional patient populations beyond its current indication.

2-(1,1-Dicyanomethylene)rhodanine-Functionalized Oligothiophenes: A Structure-Property Investigation of / Photoisomerization Behavior.

A series of oligothiophenes singly and doubly functionalized with dicyanorhodanine (RCN) units have been investigated to understand their / photoisomerization behavior upon structural modulation. Monotopic RCN target molecules (-) were designed to observe the consequences of π-conjugation, solubilizing group substitution, and formylation of the thiophene units. In all cases, the isomer is obtained from synthesis as the thermodynamically stable isomer, whereas the isomer is achieved through selective irradiation (including red light, λ = 628 nm) as a / mixture in solution.

DOK1 and DOK2 regulate CD8 T cell signaling and memory formation without affecting tumor cell killing.

Targeting intracellular inhibiting proteins has been revealed to be a promising strategy to improve CD8 T cell anti-tumor efficacy. Here, we are focusing on intracellular inhibiting proteins specific to TCR signaling: DOK1 and DOK2 expressed in T cells. We hypothesized that depletion of intracellular inhibition checkpoint DOK1 and DOK2 could improve CD8 T-cell based cancer therapies.

Structure-property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives.

Presented here is the design, synthesis, and study of a variety of novel hydrogen-bonding-capable π-conjugated -heteroacenes, 1,4-dihydropyrazino[2,3-]quinoxaline-2,3-diones (DPQDs). The DPQDs were accessed from the corresponding weakly hydrogen-bonding dicyanopyrazinoquinoxaline (DCPQ) suspensions with excess potassium hydroxide, resulting in moderate to good yields. Both families of compounds were analyzed by UV-vis and NMR spectroscopy, where the consequences of hydrogen bonding capability could be assessed through the structure-property studies.

Dicyanorhodanine-Pyrrole Conjugates for Visible Light-Driven Quantitative Photoswitching in Solution and the Solid State.

Small molecule photoswitches capable of toggling between two distinct molecular states in response to light are versatile tools to monitor biological processes, control photochemistry, and design smart materials. In this work, six novel dicyanorhodanine-based pyrrole-containing photoswitches are reported. The molecular design avails both the and isomers from synthesis, where each can be isolated using chromatographic techniques.

DR5 disulfide bonding as a sensor and effector of protein folding stress.

New agents are needed that selectively kill cancer cells without harming normal tissues. The TRAIL ligand and its receptors, DR5 and DR4, exhibit cancer-selective toxicity, but TRAIL analogs or agonistic antibodies targeting these receptors have not received FDA approval for cancer therapy. Small molecules for activating DR5 or DR4 independently of protein ligands may bypass some of the pharmacological limitations of these protein drugs.

mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.

Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTert), is expressed from the p21 locus. Expression of either TERT or TERT reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function.

Cultural adaptation and validation of the Italian version of the current relationship interview.

Background: The study of romantic relationships is based on attachment theory and the Current Relationship Interview (CRI) is a powerful tool that allows the optimal investigation of attachment representations toward romantic partners. However, evidence in this field is still unsatisfactory and further research is needed. This study aims to examine the associations between the adult attachment to partner, the style of conflict resolution, and dyadic adjustment.

Downregulation of stromal syntenin sustains AML development.

The crosstalk between cancer and stromal cells plays a critical role in tumor progression. Syntenin is a small scaffold protein involved in the regulation of intercellular communication that is emerging as a target for cancer therapy. Here, we show that certain aggressive forms of acute myeloid leukemia (AML) reduce the expression of syntenin in bone marrow stromal cells (BMSC).

A clickable melphalan for monitoring DNA interstrand crosslink accumulation and detecting ICL repair defects in Fanconi anemia patient cells.

Fanconi anemia (FA) is a genetic disorder associated with developmental defects, bone marrow failure and cancer. The FA pathway is crucial for the repair of DNA interstrand crosslinks (ICLs). In this study, we have developed and characterized a new tool to investigate ICL repair: a clickable version of the crosslinking agent melphalan which we name click-melphalan.

Rapid nanobody-based imaging of mesothelin expressing malignancies compatible with blocking therapeutic antibodies.

Introduction: Mesothelin (MSLN) is overexpressed in a wide variety of cancers with few therapeutic options and has recently emerged as an attractive target for cancer therapy, with a large number of approaches currently under preclinical and clinical investigation. In this respect, developing mesothelin specific tracers as molecular companion tools for predicting patient eligibility, monitoring then response to mesothelin-targeting therapies, and tracking the evolution of the disease or for real-time visualisation of tumours during surgery is of growing importance.

Methods: We generated by phage display a nanobody (Nb S1) and used enzymatic approaches were used to site-directed conjugate Nb S1 with either ATTO 647N fluorochrome or NODAGA chelator for fluorescence and positron emission tomography imaging (PET) respectively.

CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia.

Unlabelled: Identifying mechanisms underlying relapse is a major clinical issue for effective cancer treatment. The emerging understanding of the importance of metastasis in hematologic malignancies suggests that it could also play a role in drug resistance and relapse in acute myeloid leukemia (AML). In a cohort of 1,273 AML patients, we uncovered that the multifunctional scavenger receptor CD36 was positively associated with extramedullary dissemination of leukemic blasts, increased risk of relapse after intensive chemotherapy, and reduced event-free and overall survival.

Fast Water Transport through Subnanometer Diameter Vertically Aligned Carbon Nanotube Membranes.

Small-diameter carbon nanotubes (CNTs) have outstanding mass-transport properties, especially enhanced water flow. Here, we report on water transport through the first macroscopic membranes with vertically oriented, subnanometer (0.8 nm) CNT pores, made by a scalable, solution-based method with electric-field alignment of bulk-grown single-wall CNTs (SWCNTs).

From a drug repositioning to a structure-based drug design approach to tackle acute lymphoblastic leukemia.

Cancer cells utilize the main de novo pathway and the alternative salvage pathway for deoxyribonucleotide biosynthesis to achieve adequate nucleotide pools. Deoxycytidine kinase is the rate-limiting enzyme of the salvage pathway and it has recently emerged as a target for anti-proliferative therapies for cancers where it is essential. Here, we present the development of a potent inhibitor applying an iterative multidisciplinary approach, which relies on computational design coupled with experimental evaluations.

Niche-expressed Galectin-1 is involved in pre-B acute lymphoblastic leukemia relapse through pre-B cell receptor activation.

B-cell acute lymphoblastic leukemia (B-ALL) reflects the malignant counterpart of developing B cells in the bone marrow (BM). Despite tremendous progress in B-ALL treatment, the overall survival of adults at diagnosis and patients at all ages after relapse remains poor. Galectin-1 (GAL1) expressed by BM supportive niches delivers proliferation signals to normal pre-B cells through interaction with the pre-B cell receptor (pre-BCR).

Alexithymia in Facebook Addiction: Above and Beyond the Role of Pathological Narcissism.

Background: Personality dysfunctions and deficits in the capacity to cope with negative emotional states have been related to internet addictions. However, in relation to Facebook addiction, this issue remains poorly investigated. Specifically, few studies explored the role played by grandiose and vulnerable narcissism in Facebook addiction.

Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).

Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration.

Design, Setting, And Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.

Antimicrobial and cytotoxic effects of marine sponge extracts , and from a Caribbean Island.

Although marine sponges are known for their antimicrobial, antifungal and cytotoxic activity, very few studies have been carried out on endemic species of Martinique. Martinique is part of the Agoa Sanctuary, a marine protected area that includes the exclusive economic zones (EEZ) of the French Caribbean islands, making it an abundant source of marine species. To highlight the potential of this area for the discovery of marine biomolecules with antipathogenic and antitumor activities, we tested the aqueous and ethanolic extracts of sponge species , and .