A Competition-Based Strategy for the Isolation of an Anti-Idiotypic Blocking Module and Fine-Tuning for Conditional Activation of a Therapeutic Antibody.

The masking of therapeutic antibodies by the installation of a blocking module that can be removed under certain physiological conditions, is becoming increasingly important to improve their safety and toxicity profile. To gain access to such masking units, we used chicken immunization in combination with yeast surface display and a competition-based FACS screening campaign to obtain anti-idiotypic single-chain Fv (scFv) fragments. This approach promotes the identification of functional masking units, since specificity and high affinity do not necessarily guarantee a paratope blocking effect.

biobank.cy: the Biobank of Cyprus past, present and future.

The Cyprus Biobank collects biosamples, medical and lifestyle information with the aim of reaching 16,500 Cypriots aged ≥ 18-years, by year 2027, as part of a multitasked EU funded project. Volunteers are both from the general population and from disease cohorts of focused research projects, who amongst others will contribute to canvas the architecture of the Cyprus human genome and study the healthy and morbid anatomy of Cypriots. The Cyprus Biobank is a research infrastructure pillar of the biobank.

T cell receptor-directed antibody-drug conjugates for the treatment of T cell-derived cancers.

T cell-derived cancers are hallmarked by heterogeneity, aggressiveness, and poor clinical outcomes. Available targeted therapies are severely limited due to a lack of target antigens that allow discrimination of malignant from healthy T cells. Here, we report a novel approach for the treatment of T cell diseases based on targeting the clonally rearranged T cell receptor displayed by the cancerous T cell population.

What public health challenges and unmet medical needs would benefit from interdisciplinary collaboration in the EU? A survey and multi-stakeholder debate.

In the past decade, significant European calls for research proposals have supported translational collaborative research on non-communicable and infectious diseases within the biomedical life sciences by bringing together interdisciplinary and multinational consortia. This research has advanced our understanding of disease pathophysiology, marking considerable scientific progress. Yet, it is crucial to retrospectively evaluate these efforts' societal impact.

A Conditionally Activated Cytosol-Penetrating Antibody for TME-Dependent Intracellular Cargo Delivery.

Currently, therapeutic and diagnostic applications of antibodies are primarily limited to cell surface-exposed and extracellular proteins. However, research has been conducted on cell-penetrating peptides (CPP), as well as cytosol-penetrating antibodies, to overcome these limitations. In this context, a heparin sulfate proteoglycan (HSPG)-binding antibody was serendipitously discovered, which eventually localizes to the cytosol of target cells.

Adherence to the MIND diet and the odds of mild cognitive impairment in generally healthy older adults: The 3-year DO-HEALTH study.

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet may slow cognitive decline in older adults. A potential mechanism could be possible anti-inflammatory properties of the MIND-diet.

Objective: To examine whether adherence to the MIND diet at baseline is associated with the odds of mild cognitive impairment (MCI) and changes in biomarkers of inflammation (High-sensitivity C-reactive Protein(hsCRP), interleukin-6(IL-6)) over three years in adults ≥70 years.

Conditional activation of an anti-IgM antibody-drug conjugate for precise B cell lymphoma targeting.

Cancerous B cells are almost indistinguishable from their non-malignant counterparts regarding their surface antigen expression. Accordingly, the challenge to be faced consists in elimination of the malignant B cell population while maintaining a functional adaptive immune system. Here, we present an IgM-specific antibody-drug conjugate masked by fusion of the epitope-bearing IgM constant domain.

The first Miocene fossils from coastal woodlands in the southern East African Rift.

The Miocene was a key time in the evolution of African ecosystems witnessing the origin of the African apes and the isolation of eastern coastal forests through an expanding arid corridor. Until recently, however, Miocene sites from the southeastern regions of the continent were unknown. Here, we report the first Miocene fossil teeth from the shoulders of the Urema Rift in Gorongosa National Park, Mozambique.

Panomics reveals patient individuality as the major driver of colorectal cancer progression.

Background: Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity.

Sactipeptide Engineering by Probing the Substrate Tolerance of a Thioether-Bond-Forming Sactisynthase.

Sactipeptides are ribosomally synthesized peptides containing a unique sulfur to α-carbon crosslink. Catalyzed by sactisynthases, this thioether pattern endows sactipeptides with enhanced structural, thermal, and proteolytic stability, which makes them attractive scaffolds for the development of novel biotherapeutics. Herein, we report the in-depth study on the substrate tolerance of the sactisynthase AlbA to catalyze the formation of thioether bridges in sactipeptides.

The effect of a natural polyphenol supplement on iron absorption in adults with hereditary hemochromatosis.

Objectives: We developed a natural polyphenol supplement that strongly chelates iron in vitro and assessed its effect on non-heme iron absorption in patients with hereditary hemochromatosis (HH).

Methods: We performed in vitro iron digestion experiments to determine iron precipitation by 12 polyphenol-rich dietary sources, and formulated a polyphenol supplement (PPS) containing black tea powder, cocoa powder and grape juice extract. In a multi-center, single-blind, placebo-controlled cross-over study, we assessed the effect of the PPS on iron absorption from an extrinsically labelled test meal and test drink in patients (n = 14) with HH homozygous for the p.

Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem Cells.

Mesenchymal stem cells (MSCs) gain an increasing focus in the field of regenerative medicine due to their differentiation abilities into chondrocytes, adipocytes, and osteoblastic cells. However, it is apparent that the transformation processes are extremely complex and cause cellular heterogeneity. The study aimed to characterize differences between MSCs and cells after adipogenic (AD) or osteoblastic (OB) differentiation at the proteome level.

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Due to the large evolutionary distance between birds (Aves) und humans, immunization of chickens with human proteins results in a strong response of the bird's adaptive immune system to proteins of mammalian origin. Additionally, chicken-derived antibodies display less undesired cross-reactivity in analytical setups than conventional rodent-derived antibodies. Due to these features as well as the facile amplification of antibody-coding genes, chicken-derived antibodies emerged as promising molecules for the immunotherapy and various biotechnological applications.

Correction: Gemoll et al. Protein Profiling of Serum Extracellular Vesicles Reveals Qualitative and Quantitative Differences after Differential Ultracentrifugation and ExoQuick™ Isolation. 2020, , 1429.

The authors wish to make the following corrections to this paper [...

Single Cell Genetic Profiling of Tumors of Breast Cancer Patients Aged 50 Years and Older Reveals Enormous Intratumor Heterogeneity Independent of Individual Prognosis.

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification.

Toward Fabrication of Bioactive Papers: Covalent Immobilization of Peptides and Proteins.

Herein, we report a novel two-step method for the covalent, site-directed, and efficient immobilization of proteins on lab-made paper sheets. First, paper fibers were modified with a peptidic anchor comprising enzyme recognition motifs. Four different conjugation strategies for peptide immobilization were evaluated with respect to reproducibility and fiber loading efficiency.

Hard wiring of normal tissue-specific chromosome-wide gene expression levels is an additional factor driving cancer type-specific aneuploidies.

Background: Many carcinomas have recurrent chromosomal aneuploidies specific to the tissue of tumor origin. The reason for this specificity is not completely understood.

Methods: In this study, we looked at the frequency of chromosomal arm gains and losses in different cancer types from the The Cancer Genome Atlas (TCGA) and compared them to the mean gene expression of each chromosome arm in corresponding normal tissues of origin from the Genotype-Tissue Expression (GTEx) database, in addition to the distribution of tissue-specific oncogenes and tumor suppressors on different chromosome arms.

[Thymoma - diagnostics options].

Various types of tumors (either benign or malignant) can be found in mediastinum. Early diagnosis and treatment may help to improve survival and quality if life in these patients. Compared to direct mediastinoscopy, used for obtaining a specimen for histological analysis in previous decades, modern imaging methods, specifically the CT navigated biopsy, represent an effective and less invasive approach to the diagnosis.

Genome Instability Profiles Predict Disease Outcome in a Cohort of 4,003 Patients with Breast Cancer.

Purpose: The choice of therapy for patients with breast cancer is often based on clinicopathologic parameters, hormone receptor status, and amplification. To improve individual prognostication and tailored treatment decisions, we combined clinicopathologic prognostic data with genome instabilty profiles established by quantitative measurements of the DNA content.

Experimental Design: We retrospectively assessed clinical data of 4,003 patients with breast cancer with a minimum postoperative follow-up period of 10 years.

IgG Fc sialylation is regulated during the germinal center reaction following immunization with different adjuvants.

Background: Effector functions of IgG Abs are regulated by their Fc N-glycosylation pattern. IgG Fc glycans that lack galactose and terminal sialic acid residues correlate with the severity of inflammatory (auto)immune disorders and have also been linked to protection against viral infection and discussed in the context of vaccine-induced protection. In contrast, sialylated IgG Abs have shown immunosuppressive effects.

High Levels of Chromosomal Copy Number Alterations and TP53 Mutations Correlate with Poor Outcome in Younger Breast Cancer Patients.

Prognosis in young patients with breast cancer is generally poor, yet considerable differences in clinical outcomes between individual patients exist. To understand the genetic basis of the disparate clinical courses, tumors were collected from 34 younger women, 17 with good and 17 with poor outcomes, as determined by disease-specific survival during a follow-up period of 17 years. The clinicopathologic parameters of the tumors were complemented with DNA image cytometry profiles, enumeration of copy numbers of eight breast cancer genes by multicolor fluorescence in situ hybridization, and targeted sequence analysis of 563 cancer genes.