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APETALA 2 (ApiAP2) proteins are found in large, multisubunit regulatory complexes associated with Pf SAGA or Pf MORC. Heterochromatin-associated ApiAP2 proteins play special roles during parasite development in the blood stages. Commitment to sexual differentiation and gametocyte development and maturation are regulated by a series of ApiAP2 proteins. The regulation of gene expression in Plasmodium spp. , the causative agents of malaria, relies on precise transcriptional control. Malaria parasites encode a limited repertoire of sequence-specific transcriptional regulators dominated by the apicomplexan APETALA 2 (ApiAP2) protein family. ApiAP2 DNA-binding proteins play critical roles at all stages of the parasite life cycle. Recent studies have provided mechanistic insight into the functional roles of many ApiAP2 proteins. Two major areas that have advanced significantly are the identification of ApiAP2-containing protein complexes and the role of ApiAP2 proteins in malaria parasite sexual development. In this review, we present recent advances on the functional biology of ApiAP2 proteins and their role in regulating gene expression across the blood stages of the parasite life cycle. [ABSTRACT FROM AUTHOR]

• The study introduces a novel method for identifying DNA-binding sites using amino acid sequences. • DeepDBS uses deep learning techniques to generate representations which train a Random Forest classifier. • The study achieves high performance in accuracy (99%) in cross-validations and jackknife testing outperforming existing methods. Interactions of biological molecules in organisms are considered to be primary factors for the lifecycle of that organism. Various important biological functions are dependent on such interactions and among different kinds of interactions, the protein DNA interactions are very important for the processes of transcription, regulation of gene expression, DNA repairing and packaging. Thus, keeping the knowledge of such interactions and the sites of those interactions is necessary to study the mechanism of various biological processes. As experimental identification through biological assays is quite resource-demanding, costly and error-prone, scientists opt for the computational methods for efficient and accurate identification of such DNA-protein interaction sites. Thus, herein, we propose a novel and accurate method namely DeepDBS for the identification of DNA-binding sites in proteins, using primary amino acid sequences of proteins under study. From protein sequences, deep representations were computed through a one-dimensional convolution neural network (1D-CNN), recurrent neural network (RNN) and long short-term memory (LSTM) network and were further used to train a Random Forest classifier. Random Forest with LSTM-based features outperformed the other models, as well as the existing state-of-the-art methods with an accuracy score of 0.99 for self-consistency test, 10-fold cross-validation, 5-fold cross-validation, and jackknife validation while 0.92 for independent dataset testing. It is concluded based on results that the DeepDBS can help accurate and efficient identification of DNA binding sites (DBS) in proteins. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the second most deathly worldwide and third most common cancer, CRC is a very heterogeneous disease where tumors can form by both environmental and genetic risk factors and includes epigenetic and genetic alternations. Inhibitors of DNA binding proteins (ID) are a class of helix-loop-helix transcription regulatory factors; these proteins are considered a family of four highly preserved transcriptional regulators (ID1-4), shown to play significant roles in many processes that are associated with tumor development. ID family plays as negatively dominant antagonists of other essential HLH proteins, concluding the creation of non-functional heterodimers and regulation of the transcription process. Materials and methods: 120 Fresh tissue and blood samples Forty (40) samples of fresh tissue and blood were collected from patients diagnosed with CRC, twenty (20) samples were collected from a patient diagnosed as healthy. The (qRT-PCR) method is a sensitive technique for the quantifying of steady-state mRNA levels that used to evaluation the expression levels of ID (1–4) gene. Results: The findings indicate downregulation in ID1 in tissue with a highly significant change between patients and control groups, where upregulation in the ID1 gene is shown in blood samples.ID2 gene also demonstrated high significant change where show upregulation in tissue and downregulation in blood sample. ID3 and ID4 genes show downregulation in tissue and blood samples with a significant change in ID3 blood samples between patient and blood groups. Conclusion: Because of the regulation function of the ID family in many processes, the up or down regulation of IDs genes in tumors Proves how important its tumor development, and therefore those proteins can be used as an indicator for CRC. [ABSTRACT FROM AUTHOR]

* Context.--Pituitary neuroendocrine tumors/adenomas are common intracranial tumors that require accurate subtyping because each tumor differs in its biologic behavior and response to treatment. Pituitary-specific transcription factors allow for improved lineage identification and diagnosis of newly introduced variants. Objective.--To assess the usefulness of transcription factors and design a limited panel of immunostains for classification of pituitary neuroendocrine tumors/adenoma. Design.--A total of 356 tumors were classified as per expression of pituitary hormones and transcription factors T-box family member TBX19 (TPIT), pituitary-specific POU-class homeodomain (PIT1), and steroidogenic factor-1 (SF-1). The resultant classification was correlated with patients' clinical and biochemical features. The performance and relevance of individual immunostains were analyzed. Results.--Reclassification of 34.8% (124 of 356) of pituitary neuroendocrine tumors/adenoma was done after application of transcription factors. The highest agreement with final diagnosis was seen using a combination of hormone and transcription factors. SF-1 had higher sensitivity, specificity, and predictive value compared with follicle-stimulating hormone and luteinizing hormone. On the other hand, TPIT and PIT1 had similar performance and Allred scores compared with their respective hormones. Conclusions.--SF-1 and PIT1 should be included in the routine panel for guiding the classification. PIT1 positivity needs to be followed by hormone immunohistochemistry, especially in nonfunctional cases. TPIT and adrenocorticotropin can be used interchangeably as per availability of the lab. (Arch Pathol Lab Med. 2024;148:178-189; doi: 10.5858/arpa.2021-0479-OA), Pituitary adenomas (PAs) or pituitary neuroendocrine tumors (pitNETs) are common intracranial tumors, third only to meningioma and gliomas. (1) Pituitary transcription factors (PTFs) play a well-established and dominant role in [...]

The potato (Solarium tuberosum) is the fourth most cultivated and consumed crop worldwide. The swelled stolonic region of the plant is economically important due to its considerable quantities of carbohydrates plus modest quantities of minerals and vitamins. Tuber formation is governed by various external and internal factors including light, oxygen concentration, photosynthate availability, phytochromes, transcription factors, and metabolite availability. This review updates and expands upon our current knowledge regarding the involvement of these variables in the tuberization process. Tuber formation starts at the onset of the supportive season under optimal light conditions where phytochromes in leaves sense the signal. The transmittance of the signal results in photosynthate accumulation, phloem loading with sucrose, phloem transport and unloading at the stolonic region, sucrose entry into the tuber cell, and conversion of sucrose to starch, all under the direction of regulatory enzymes. Several genes are associated with tuberization and regulated either positively or negatively. During the course of these cellular micro-reactions, a very fine stolonic tip will ultimately be transformed into a fully matured potato tuber. Tuber formation can be increased by genetic modifications, that further improve tuber yield and quality. Keywords Gene * Light * Oxygen * Phytochromes * Starch, Introduction The potato tuber functions as a reservoir for a variety of macromolecules, in particular starches and proteins. Potato tuberization (TB) is a complex developmental process involving the coordination of [...]

• XPA is an essential protein for the repair of bulky DNA lesions through Nucleotide Excision Repair. • XPA works in complex with RPA to orient the DNA for processing. • A site-specific Cy3 fluorophore was incorporated on XPA and reports on ssDNA binding dynamics. • Detailed methods to generate fluorescent XPA and conditions to generate and maintain stable protein are described. Nucleotide excision repair (NER) promotes genomic integrity by removing bulky DNA adducts introduced by external factors such as ultraviolet light. Defects in NER enzymes are associated with pathological conditions such as Xeroderma Pigmentosum, trichothiodystrophy, and Cockayne syndrome. A critical step in NER is the binding of the Xeroderma Pigmentosum group A protein (XPA) to the ss/ds DNA junction. To better capture the dynamics of XPA interactions with DNA during NER we have utilized the fluorescence enhancement through non-canonical amino acids (FEncAA) approach. 4-azido- L -phenylalanine (4AZP or pAzF) was incorporated at Arg-158 in human XPA and conjugated to Cy3 using strain-promoted azide-alkyne cycloaddition. The resulting fluorescent XPA protein (XPACy3) shows no loss in DNA binding activity and generates a robust change in fluorescence upon binding to DNA. Here we describe methods to generate XPACy3 and detail in vitro experimental conditions required to stably maintain the protein during biochemical and biophysical studies. [ABSTRACT FROM AUTHOR]

Certain respiratory fungal pathogen mono-infections can cause high mortality rates. Several viral pathogen mono-infections, including influenza viruses and coronaviruses including SARS-CoV-2, can also cause high mortality rates. Concurrent infections by fungal pathogens and highly manipulative viral pathogens can synergistically interact in the respiratory tract to substantially increase their mortality rates. There are at least five viral manipulations which can assist secondary fungal infections. These viral manipulations include the following: (1) inhibiting transcription factors and cytokine expressions, (2) impairing defensive protein expressions, (3) inhibiting defenses by manipulating cellular sensors and signaling pathways, (4) inhibiting defenses by secreting exosomes, and (5) stimulating glucocorticoid synthesis to suppress immune defenses by inhibiting cytokine, chemokine, and adhesion molecule production. The highest mortality respiratory viral pandemics up to now have had substantially boosted mortalities by inducing secondary bacterial pneumonias. However, numerous animal species besides humans are also carriers of endemic infections by viral and multidrug-resistant fungal pathogens. The vast multi-species scope of endemic infection opportunities make it plausible that the pro-fungal manipulations of a respiratory virus can someday evolve to enable a very high mortality rate viral pandemic inducing multidrug-resistant secondary fungal pathogen infections. Since such pandemics can quickly spread world-wide and outrun existing treatments, it would be worthwhile to develop new antifungal treatments well before such a high mortality event occurs., Author(s): Kevin Roe [sup.1] Author Affiliations: (1) USPTO, , San Jose, CA, USA Introduction Several viral and fungal pathogens can cause severe mono-infections in humans [1-4]. Furthermore, certain types of [...]