bluuebunny/crossref_metadata_2025 huggingface dataset:
Acacia Zeneida Kuenzer
Authors: Urbanetz Sandra Terezinha , Barreiro Cristhianny
Published: April 2024

Este artigo é sobre a obra de Acacia Zeneida Kuenzer, importante referência feminina para pensar a formação de professores, especialmente a da Educação Profissional.  Através da análise de artigos e de entrevista realizada com a autora, pode-se inferir que desde a década de 1980, a autora defende uma formação docente que se dê em um espaço universitário, tendo em vista a articulação dos conhecimentos sobre o mundo do trabalho e aos científico-tecnológicos de todas as áreas de conhecimento, através de práticas integradas e integradoras entre ciência, cultura e trabalho, dentro dos eixos contextual, institucional, pedagógico, práxico, ético, e investigativo. Também é possível perceber em sua obra, o posicionamento da formação docente na relação com o trabalho e com a educação, demonstrando que a precarização do trabalho e da formação docente servem ao que chama de inclusão excludente, uma vez que fazem ingressar no sistema educacional os trabalhadores e seus filhos sem dotá-los de efetivas condições de análise e transformação social, em um movimento que vem se aprofundando de redução dos conhecimentos teóricos em benefício dos conhecimentos instrumentais e pragmáticos. Kuenzer aponta como a educação acaba por servir a manutenção e aprofundamento das relações de exploração capitalista, tornando ainda mais necessário ao papel do professor refletir e fazer refletir as condições que permeiam o mundo do trabalho, amparado em sólido ferramental teórico que permita a ação em direção a uma sociedade mais justa.  A vida e obra acadêmica da autora são exemplos de militância em prol desses objetivos.
Relações, métodos, palavras
Authors: Ferreira Luciana Haddad , Soares Neuzita de Paula , Aguiar Thiago Borges de
Published: April 2024

O estudo aqui apresentado tem como objetivo discutir as contribuições de Maria Helena Menna Barreto Abrahão, professora e pesquisadora, para a investigação narrativa (auto)biográfica e para o campo de estudos da formação docente. Valemo-nos, para tanto, da mesma premissa defendida por Maria Helena em toda a sua trajetória: colocamos a vida no centro do processo e tomamos como objeto de estudo e reflexão sua própria narrativa (auto)biográfica. Para análise, apresentamos excertos da narrativa da pesquisadora, produzida no contexto de uma entrevista narrativa, enfatizando as articulações entre a formação de professoras e o paradigma (auto)biográfico de produção do conhecimento sobre educação. Dentre diferentes aspectos apresentados na narrativa, destacamos três dimensões. Na primeira, as relações, entendemos que a pesquisa e seu campo só existem no espaço da interlocução. Na segunda, os métodos, compreendemos as diferenças entre paradigmas pautados pelo recorte da realidade e o paradigma aqui discutido que está aberto ao inédito do momento da pesquisa. Na terceira, as palavras, observamos como termos consolidados no campo investigativo vão se modificando como resultado de uma interação humana. O estudo também reconhece a contribuição da pesquisadora para o fortalecimento das bases teóricas das pesquisas (auto)biográficas. O trabalho investigativo de vanguarda dessa mulher brasileira abriu caminhos para um movimento de pesquisa que tem contribuído significativamente para a formação e valorização docente no país.
A CONTRIBUTION TO THE KNOWLEDGE ON BIOLOGICAL DIVERSITY OF THE JEZERAČKA RIVER (THE REPUBLIC OF SRPSKA, BOSNIA AND HERZEGOVINA)
Authors: Golub Dragojla , Dekić Radoslav , Lolić Svjetlana , Dmitrović Dejan , Lubarda Biljana
Published: April 2024

Analyses of physical, chemical and biological parameters of the Jezeračka River were conducted in 2020. Given that the planning documents of the Republic of Srpska recognized these natural spawning grounds of Salmo trutta as a potentially protected zone, the aim of the paper was to evaluate ecological and biological water properties of our target river and its surrounding area. Following the application of standard methods, biological research covered microbiological analyses and the analyses of phytobenthos, periphyton, macrozoobenthos, ichthyofauna and flora. Values of the analyzed physical-chemical and sanitary-microbiological parameters suggested that the water quality of the Jezeračka River was 1st class. Analyses based on the qualitative and quantitative composition of the phytobenthos, periphyton, macrozoobenthos and ichthyofauna community indicated that the water was of the 1st class quality and qualified for the high ecological status. The well-preserved autochthonous flora and vegetation along the riverbank are favorable to the water quality maintenance. Results imply that biological and ecological conditions are suitable for life and spawning of Salmo trutta and that the upper Jezeračka River stream, the natural spawning grounds of the species, meets all requirements to preserve and improve Salmo trutta population.
ОДРЕЂИВАЊЕ САДРЖАЈА ХЛОРИДА У ФЛАШИРАНОЈ МИНЕРАЛНОЈ ВОДИ
Authors: Благојевић Драгана , Половина Андреа , Лазић Драгица , Јелић Дијана
Published: April 2024

Минералне воде са различитих извора имају различит садржај, јер сваки извор има своје посебне физичко-хемијске карактеристике. Хлориди се појављују у природним водама као посљедица растварања минерала из седимената, али и као посљедица антропогеног утицаја. У оквиру овог рада кориштена је Морова (Mohr) метода одређивања садржаја хлорида. За испитивање су кориштене природне минералне воде „aqua viva” и „ELEMENT”. Одређивање Моровом методом вршено је у узорцима воде без додатка стандарда и са додатком стандарда, као и у самим стандардима. У узорцима воде без додатка стандарда добијене су много веће вриједности садржаја хлорида од оних датих декларацијом. Резултатима Recovery теста, добијеним након одређивања садржаја хлорида у узорцима са додатком стандарда потврђена је примијењена метода за кориштени опсег концентрација. На основу разлике у садржају хлорида у узорцима са додатком стандарда и самим стандардима одређене су вриједности садржаја хлорида у узорку и оне су биле ближе вриједностима наведеним на декларацији. Узимајући у обзир резултате изведених анализа, може се рећи да се они слажу са подацима из литературе, тј. Морова метода погоднија је за одређивање у узорцима са великим концентрацијама хлорида. Код узорака који садрже мале концентрације хлорида, забиљежена је тенденција ка повећаним резултатима, што је био случај и у овом истраживању.
CHROMOSOMAL ABERRATIONS IN COUPLES WITH STERILITY AND HABITUAL ABORTIONS AT THE UNIVERSITY CLINICAL CENTER OF THE REPUBLIC OF SRPSKA
Authors: Ivanković Branislava , Paraš Smiljana
Published: April 2024

The cytogenetic laboratory of the University Clinical Center of the Republic of Srpska (UCCRS) in Banja Luka is the primary institution where the karyotypes of patients’ peripheral blood are analyzed. In the period from 2009 to 2019, a total of 3842 karyotype analyzes of patients were performed in it, of which 1956 had a referral diagnosis of sterility and habitual abortion, and therefore the inability to achieve pregnancy. The importance of cytogenetic analysis of patient’s karyotypes is great because the presence of chromosomal aberrations in them can be the cause of sterility and spontaneous abortions in patients. Therefore, the aim of the work was to determine the presence of chromosomal aberrations in the karyotypes of patients at the University Hospital of RS who had a referral diagnosis of sterility or habitual abortion. The total number of processed karyotype samples of patients in the Cytogenetic Laboratory at the UCCRS in the period from 2009 to 2019 grew by year. The study found a significant difference in the frequency distribution of patients with a diagnosis of sterility, which was twice as many as compared to patients with a diagnosis of habitual abortion. The percentage of patients who are treated for sterility and habitual abortion with the presence of chromosomal aberrations in their karyotypes compared to those without aberrations is on average low. An equal distribution of male and female patients with aberrant karyotypes who were treated for sterility and habitual abortions was determined. The most prevalent chromosomal aberrations in the karyotypes of both male and female patients treated for sterility and habitual abortion were inversions, followed by mosaic aberrations, then translocations; then followed by trisomies, Robertsonian translocations and finally additions.
SADRŽAJ NITRATA I AKTIVNOST NITRAT-REDUKTAZE U POVRĆU UZETOM SA „TRŽNICE“ U BANJOJ LUCI I PROCJENE RIZIKA
Authors: Maksimović Tanja , Manojlović Maja , Dekić Radoslav
Published: April 2024

Visok sadržaj nitrata i nitrita u povrću može imati toksične i kancerogene efekte na ljudski organizam, te je neophodno praćenje kako bi se primijenile odgovarajuće zaštitne mjere. Cilj istraživanja u ovom radu bio je određivanje sadržaja nitrata i praćenje aktivnosti nitrat-reduktaze u povrću (blitva, mrkva, peršun, kupus) uzetom sa različitih štandova gradske tržnice u Banjoj Luci. Prosječna koncentracija nitrata u uzorcima povrća kretala se od 1 do 650 mgkg-1, pri čemu su najveće vrijednosti dobijene u blitvi i kupusu, a najniže u korijenu peršuna. Aktivnost nitrat-reduktaze bila je povećana u blitvi, dok je najniža utvrđena u korijenu peršuna. Sadržaj nitrata u uzorcima povrća bio je u granicama koje su propisane od strane Svjetske zdravstvene organizacije, tako da ne postoji potencijalna opasnost po zdravlje ljudi.
ICHTHYOFAUNA OF LOWER PART OF THE VRBANJA RIVER (THE REPUBLIC OF SRPSKA, BiH)
Authors: Cvijić Svjetlana , Golub Dragojla , Šukalo Goran , Dekić Radoslav , Kostić Desanka , Miljanović Branko , Kanlić Vera
Published: April 2024

The diversity of freshwater ichthyofauna of Bosnia and Herzegovina (BiH) covers about 117 fish species/subspecies and makes up about 20% of European freshwater ichthyofauna. The Vrbanja River Basin is located in the central part of Bi and is one of the indigenous basins in the Republic of Srpska. The Vrbanja River is one of the largest right tributaries of the Vrbas River, with the lower part of the stream stretching for about 28 km. Ichthyological research of the lower part of the Vrbanja River was conducted during 2013, at three locations, and the sampling was performed with an electric fishing device ELT 62 II GI, 3 kW. The qualitative and quantitative compositions of ichthyofauna as well as some diversity indices (Simpson index, Shannon-Weaver index, Dominance index and Sørensen similarity index) were determined. The lower stream of the Vrbanja River is inhabited by 10 fish species belonging to three families (Cyprinidae, Cobitidae and Percidae). Family Cyprinidae is typified by the largest species diversity. The species dominant in terms of number of individuals and biomass were Barbus balcanicus and Squalius cephalus, which differ greatly from the ichthyofauna that inhabited the same area in the mid-20th century. This composition of ichthyofauna of the lower part of the Vrbanja River is related to the environmental factors and impact of certain human activities.
Tactical bases of fire training of cadets and students of educational organizations of the Ministry of Internal Affairs of Russia
Authors: Vasil'ev Mikhail Aleksandrovich , Kleimenov Semen Yur'evich
Published: April 2024

The object of the research of the scientific article is the tactical basics of handling firearms during fire training. The subject of the study is the methods that develop the tactical basics of firearm ownership in the training of fire training. The aim of the study is to identify the most effective methods for conducting fire training classes aimed at developing tactical skills in handling firearms. Research objective is to determine the most effective and accessible methods in the process of handling firearms. The practical significance of the conducted research is to identify the most effective methods for training fire training, necessary for practical application. At the same time, attention is paid to strict compliance with safety measures when handling both training and combat weapons. The methodology of the conducted research is determined by its purpose and objectives. It is based on a systematic approach to the study of methods of training police officers in the practical use of firearms. The novelty of the scientific article lies in the development of author's methods in the study and testing of tactical actions of cadets and students of educational organizations of the Ministry of Internal Affairs of Russia in the handling of firearms during practical training. The training exercises were practically tested during the training of cadets and trainees at the initial stage of the practical part of fire training, during the development of tactical skills, it was carried out both idling and during combat shooting from small arms. The development of tactical actions with firearms allowed the trainees to form confident practical skills in handling firearms, which in turn affected the increase in the level of general discipline and the readiness of employees to act in practice.
In vitro studies on curcumin-loaded multiwalled carbon nanotubes antioxidant activities and cytotoxicity against Hep G-2 liver cancer cell lines
Authors: Rabba’a Manar , Abu-Zurayk Rund , Abu-Irmaileh Bashaer , Mallouh Saida Abu , Bustanji Yasser
Published: April 2024

Many nanoscale drug delivery systems have been evaluated for their excellent properties, such as carbon nanotubes; however, due to their hydrophobic nature, surface modification or functionalization is the major step to prepare a biocompatible and well-dispersed multiwalled carbon nanotubes (MWCNTs) in biological fluids. This study aims to noncovalently functionalize MWCNT with chitosan to deliver curcumin to liver cancer cell lines and to investigate their in vitro cell cytotoxicity and antioxidant activity. The conjugation between chitosan, MWCNT, and curcumin was confirmed using Fourier transform infrared spectroscopy, Brunauer–Emmett–Teller surface area, pore size analysis, scanning electron microscopy, and thermogravimetric analysis. It was found that curcumin-chitosan- MWCNT had the highest entrapment efficiency of 99.1%. The average surface area of curcumin-chitosan-MWCNT was 52.73 m2/g, which showed more than 80% antioxidant activity for all used concentrations using 2,2-Diphenyl-1- picrylhydrazyl and 2,2′ azinobis, 3-ethylbenzothiazoline-6-sulphonic acid methods. The IC 50 of curcumin-chitosan- MWCNT used on the Hep G2 liver cell line was 43.62 μg/ml, while it was 227.6 μg/ml when used on fibroblast. In conclusion, the combination of curcumin, chitosan, and MWCNT showed a considerable reduction in cancer cell viability, and curcumin-chitosan-MWCNT can be proposed as a biocompatible carrier for liver cancer treatment.
Phenolic compounds in grapes (genus Vitis): A review of their antioxidant activity, antiproliferative capacity, and cytotoxic effect on colorectal cancer
Authors: Neira-Ospina Estefanía , Rojas Jessica , Santa-Gonzalez Gloria A. , Garzón Maritza Andrea Gil
Published: April 2024

In the pursuit of potent antioxidant sources for potential health benefits, significant attention has been directed toward polyphenols. This research is especially relevant in the context of colorectal cancer (CRC), a widespread and deadly malignancy. The exploration of preventive strategies has led to a growing interest in grapes and their derivatives, such as juices and wines, which offer various consumption options based on grape type. This investigation encompasses a comprehensive analysis of multiple grape components: skin, pulp, seed, pomace, wine, juice, and extracts. These assessments serve as a critical reference for exploring functional ingredients from grapes and their potential as chemopreventive agents against colon cancer. This scientific literature review aims to provide an in-depth overview of advancements from 2012 to 2023. A systematic review reveals varying polyphenol concentrations in different grape components and their correlation with antioxidant capacities. In addition, the chemical profiles of these matrices are analyzed concerning their antioxidant properties, antiproliferative effects, and cytotoxicity, validated through in vitro and in vivo models simulating CRC scenarios. This research seeks to demonstrate grapes’ potential, in their diverse forms, as promising functional food options.
New bisnorsesquiterpene from Glottiphyllum linguiforme and its antimicrobial, cytotoxic, and antioxidant activities
Authors: Ahmed Hayam S. , Amir Dalia El , Muhaisen Hasan M. H. , Sebak Mohamed , Abdelghany Tamer M. , Elmaidomy Abeer H. , Amin Elham , Owis Asmaa I. , A. Orabi Mohamed A. , Afifi Naglaa
Published: April 2024

Natural product research is a cornerstone in the drug discovery process. Many inspiring chemical moieties with new skeletons and potent biological activity are commonly reported from natural sources. Chromatographic examination of the alcoholic extract of Glottiphyllum linguiforme aerial furnished four compounds, including β-sitosterol (1), β-sitosterol-3-O-β-D-glucopyranoside (2), and 1,1′ biuracil (3), and a new compound, tectoionyl A 3-O-sodium sulfate (4). The new structure was elucidated using high-resolution mass and intensive 1D and 2D NMR spectroscopic analyses. Quantitative analysis of G. linguiforme extract revealed considerable contents of total phenolic and total flavonoid. A DPPH antioxidant assay indicated moderate activity (0.026 mg acid equivalent antioxidant capacity/g dry extract). Antimicrobial activity testing of the pure compounds indicated noticeable antibacterial activity of compound 2 against Escherichia coli, Salmonella enterica, and Pseudomonas aeruginosa. In addition, compounds 1–4 displayed mild cytotoxic effects against human breast adenocarcinoma (MCF7) and hepatocellular carcinoma (HepG2) cell lines, and the normal (Vero) cells at the tested concentration (100 μg/ml), as compared to the standard cytotoxic drug, doxorubicin. This study is the first to estimate phenolics and flavonoid contents, discover constituents by phytochemical isolation, and examine cytotoxicity and antimicrobial properties of G. linguiforme. The unusual nitrogenous compound 1,1′-biuracil (3) and the sulfate derivative (4) may evidence chemotaxonomic importance.
MEMO1 binds iron and modulates iron homeostasis in cancer cells
Authors: Dolgova Natalia , Uhlemann Eva-Maria E , Boniecki Michal T , Vizeacoumar Frederick S , Ara Anjuman , Nouri Paria , Ralle Martina , Tonelli Marco , Abbas Syed A , Patry Jaala , Elhasasna Hussain , Freywald Andrew , Vizeacoumar Franco J , Dmitriev Oleg Y
Published: April 2024

Mediator of ERBB2-driven cell motility 1 (MEMO1) is an evolutionary conserved protein implicated in many biological processes; however, its primary molecular function remains unknown. Importantly, MEMO1 is overexpressed in many types of cancer and was shown to modulate breast cancer metastasis through altered cell motility. To better understand the function of MEMO1 in cancer cells, we analyzed genetic interactions of MEMO1 using gene essentiality data from 1028 cancer cell lines and found multiple iron-related genes exhibiting genetic relationships with MEMO1. We experimentally confirmed several interactions between MEMO1 and iron-related proteins in living cells, most notably, transferrin receptor 2 (TFR2), mitoferrin-2 (SLC25A28), and the global iron response regulator IRP1 (ACO1). These interactions indicate that cells with high-MEMO1 expression levels are hypersensitive to the disruptions in iron distribution. Our data also indicate that MEMO1 is involved in ferroptosis and is linked to iron supply to mitochondria. We have found that purified MEMO1 binds iron with high affinity under redox conditions mimicking intracellular environment and solved MEMO1 structures in complex with iron and copper. Our work reveals that the iron coordination mode in MEMO1 is very similar to that of iron-containing extradiol dioxygenases, which also display a similar structural fold. We conclude that MEMO1 is an iron-binding protein that modulates iron homeostasis in cancer cells.
The (Limited?) Utility of Brain Age as a Biomarker for Capturing Fluid Cognition in Older Individuals
Authors: Tetereva Alina , Pat Narun
Published: April 2024

Fluid cognition usually declines as people grow older. For decades, neuroscientists have been on a quest to search for a biomarker that can help capture fluid cognition. One well-known candidate is Brain Age, or a predicted value based on machine-learning models built to predict chronological age from brain MRI data. Here we aim to formally evaluate the utility of Brain Age as a biomarker for capturing fluid cognition among older individuals. Using 504 aging participants (36-100 years old) from the Human Connectome Project in Aging, we created 26 age-prediction models for Brain Age based on different combinations of MRI modalities. We first tested how much Brain Age from these age-prediction models added to what we had already known from a person’s chronological age in capturing fluid cognition. Based on the commonality analyses, we found a large degree of overlap between Brain Age and chronological age, so much so that, at best, Brain Age could uniquely add only around 1.6% in explaining variation in fluid cognition. Next, the age-prediction models that performed better at predicting chronological age did NOT necessarily create better Brain Age for capturing fluid cognition over and above chronological age. Instead, better-performing age-prediction models created Brain Age that overlapped larger with chronological age, up to around 29% out of 32%, in explaining fluid cognition, thus not improving the models’ utility to capture cognitive abilities. Lastly, we tested how much Brain Age missed the variation in the brain MRI that could explain fluid cognition. To capture this variation in the brain MRI that explained fluid cognition, we computed Brain Cognition, or a predicted value based on prediction models built to directly predict fluid cognition (as opposed to chronological age) from brain MRI data. We found that Brain Cognition captured up to an additional 11% of the total variation in fluid cognition that was missing from the model with only Brain Age and chronological age, leading to around a 1/3-time improvement of the total variation explained. Accordingly, we demonstrated the limited utility of Brain Age as a biomarker for fluid cognition and made some suggestions to ensure the utility of Brain Age in explaining fluid cognition and other phenotypes of interest.
The CD4 transmembrane GGXXG and juxtamembrane (C/F)CV+C motifs mediate pMHCII-specific signaling independently of CD4-LCK interactions
Authors: Lee Mark S , Tuohy Peter J , Kim Caleb Y , Yost Philip P , Lichauco Katrina , Parrish Heather L , Van Doorslaer Koenraad , Kuhns Michael S
Published: April 2024

CD4+ T cell activation is driven by five-module receptor complexes. The T cell receptor (TCR) is the receptor module that binds composite surfaces of peptide antigens embedded within MHCII molecules (pMHCII). It associates with three signaling modules (CD3γε, CD3δε, and CD3ζζ) to form TCR-CD3 complexes. CD4 is the coreceptor module. It reciprocally associates with TCR-CD3-pMHCII assemblies on the outside of a CD4+ T cells and with the Src kinase, LCK, on the inside. Previously, we reported that the CD4 transmembrane GGXXG and cytoplasmic juxtamembrane (C/F)CV+C motifs found in eutherian (placental mammal) CD4 have constituent residues that evolved under purifying selection (Lee et al., 2022). Expressing mutants of these motifs together in T cell hybridomas increased CD4-LCK association but reduced CD3ζ, ZAP70, and PLCγ1 phosphorylation levels, as well as IL-2 production, in response to agonist pMHCII. Because these mutants preferentially localized CD4-LCK pairs to non-raft membrane fractions, one explanation for our results was that they impaired proximal signaling by sequestering LCK away from TCR-CD3. An alternative hypothesis is that the mutations directly impacted signaling because the motifs normally play an LCK-independent role in signaling. The goal of this study was to discriminate between these possibilities. Using T cell hybridomas, our results indicate that: intracellular CD4-LCK interactions are not necessary for pMHCII-specific signal initiation; the GGXXG and (C/F)CV+C motifs are key determinants of CD4-mediated pMHCII-specific signal amplification; the GGXXG and (C/F)CV+C motifs exert their functions independently of direct CD4-LCK association. These data provide a mechanistic explanation for why residues within these motifs are under purifying selection in jawed vertebrates. The results are also important to consider for biomimetic engineering of synthetic receptors.
A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice
Authors: Shaku Moagi Tube , Um Peter K , Ocius Karl L , Apostolos Alexis J , Pires Marcos M , Bishai William R , Kana Bavesh D
Published: April 2024

Mechanisms by which Mycobacterium tuberculosis (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position in peptidoglycan side-chains. As the current BCG vaccine is derived from pathogenic mycobacteria, a similar situation prevails. To alleviate this masking ability and to potentially improve efficacy of the BCG vaccine, we used CRISPRi to inhibit expression of the essential enzyme pair, MurT-GatD, implicated in amidation of peptidoglycan side-chains. We demonstrate that depletion of these enzymes results in reduced growth, cell wall defects, increased susceptibility to antibiotics, altered spatial localization of new peptidoglycan and increased NOD-1 expression in macrophages. In cell culture experiments, training of a human monocyte cell line with this recombinant BCG yielded improved control of Mtb growth. In the murine model of TB infection, we demonstrate that depletion of MurT-GatD in BCG, which is expected to unmask the D-glutamate diaminopimelate (iE-DAP) NOD-1 ligand, yields superior prevention of TB disease compared to the standard BCG vaccine. In vitro and in vivo experiments in this study demonstrate the feasibility of gene regulation platforms such as CRISPRi to alter antigen presentation in BCG in a bespoke manner that tunes immunity towards more effective protection against TB disease.
Mono-methylated histones control PARP-1 in chromatin and transcription
Authors: Bamgbose Gbolahan , Bordet Guillaume , Lodhi Niraj , Tulin Alexei
Published: April 2024

PARP-1 is central to transcriptional regulation under both normal and stress conditions, with the governing mechanisms yet to be fully understood. Our biochemical and ChIP-seq-based analyses showed that PARP-1 binds specifically to active histone marks, particularly H4K20me1. We found that H4K20me1 plays a critical role in facilitating PARP-1 binding and the regulation of PARP-1-depenednt loci during both development and heat shock stress. Here we report that the sole H4K20 mono-methylase,
pr-set7
, and
parp-1 Drosophila
mutants undergo developmental arrest. RNA-seq analysis showed an absolute correlation between PR-SET7- and PARP-1-dependent loci expression, confirming co-regulation during developmental phases. PARP-1 and PR-SET7 are both essential for activating
hsp70
and other heat shock genes during heat stress, with a notable increase of H4K20me1 at their gene body. Mutating
pr-set7
disrupts monometylation of H4K20 along heat shock loci and abolish PARP-1 binding there. These data strongly suggest that H4 monometylation is a key triggering point in PARP-1 dependent processes in chromatin.
Structural and dynamic changes in P-Rex1 upon activation by PIP3 and inhibition by IP4
Authors: Ravala Sandeep K. , Adame-Garcia Sendi Rafael , Li Sheng , Chen Chun-Liang , Cianfrocco Michael A. , Gutkind J. Silvio , Cash Jennifer N. , Tesmer John J. G.
Published: April 2024

PIP
3
-dependent Rac exchanger 1 (P-Rex1) is abundantly expressed in neutrophils and plays central roles in chemotaxis and cancer metastasis by serving as a guanine-nucleotide exchange factor (GEF) for Rac. The enzyme is synergistically activated by PIP
3
and the heterotrimeric Gβγ subunits, but mechanistic details remain poorly understood. While investigating the regulation of P-Rex1 by PIP
3
, we discovered that Ins(1,3,4,5)P
4
(IP
4
) inhibits P-Rex1 activity and induces large decreases in backbone dynamics in diverse regions of the protein. Cryo-electron microscopy analysis of the P-Rex1·IP
4
complex revealed a conformation wherein the pleckstrin homology (PH) domain occludes the active site of the Dbl homology (DH) domain. This configuration is stabilized by interactions between the first DEP domain (DEP1) and the DH domain and between the PH domain and a 4-helix bundle (4HB) subdomain that extends from the C-terminal domain of P-Rex1. Disruption of the DH–DEP1 interface in a DH/PH-DEP1 fragment enhanced activity and led to a more extended conformation in solution, whereas mutations that constrain the occluded conformation led to decreased GEF activity. Variants of full-length P-Rex1 in which the DH–DEP1 and PH–4HB interfaces were disturbed exhibited enhanced activity during chemokine-induced cell migration, confirming that the observed structure represents the autoinhibited state in living cells. Interactions with PIP
3
-containing liposomes led to disruption of these interfaces and increased dynamics protein-wide. Our results further suggest that inositol phosphates such as IP
4
help to inhibit basal P-Rex1 activity in neutrophils, similar to their inhibitory effects on phosphatidylinositol-3-kinase.
De novo variants in PLCG1 are associated with hearing impairment, ocular pathology, and cardiac defects
Authors: Ma Mengqi , Zheng Yiming , Lu Shenzhao , Pan Xueyang , Worley Kim C. , Burrage Lindsay C. , Blieden Lauren S. , Allworth Aimee , Chen Wei-Liang , Merla Giuseppe , Mandriani Barbara , Rosenfeld Jill A. , Li-Kroeger David , Dutta Debdeep , Yamamoto Shinya , Wangler Michael F. ,   Undiagnosed Diseases Network, Glass Ian A. , Strohbehn Sam , Blue Elizabeth , Prontera Paolo , Lalani Seema R. , Bellen Hugo J.
Published: April 2024

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and diacylglycerol, important signaling molecules involved in many cellular processes.
PLCG1
encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of
PLCG1
are observed in multiple cancers, but only one germline variant has been reported. Here we describe three unrelated individuals with
de novo
heterozygous missense variants in
PLCG1
(p.Asp1019Gly, p.His380Arg, and p.Asp1165Gly) who exhibit variable phenotypes including hearing loss, ocular pathology and cardiac septal defects. To model these variants
in vivo
, we generated the analogous variants in the
Drosophila
ortholog,
small wing
(
sl
). We created a null allele

sl
T2A

and assessed the expression pattern.
sl
is broadly expressed, including in wing discs, eye discs, and a subset of neurons and glia. Loss of
sl
causes wing size reductions, ectopic wing veins and supernumerary photoreceptors. We document that mutant flies exhibit a reduced lifespan and age-dependent locomotor defects. Expressing wild-type
sl
in

sl
T2A

mutant rescues the loss-of-function phenotypes whereas expressing the variants causes lethality. Ubiquitous overexpression of the variants also reduces viability, suggesting that the variants are toxic. Ectopic expression of an established hyperactive
PLCG1
variant (p.Asp1165His) in the wing pouch causes severe wing phenotypes, resembling those observed with overexpression of the p.Asp1019Gly or p.Asp1165Gly variants, further arguing that these two are gain-of-function variants. However, the wing phenotypes associated with p.His380Arg overexpression are mild. Our data suggest that the
PLCG1 de novo
heterozygous missense variants are pathogenic and contribute to the features observed in the probands.
Endocannabinoids and their receptors modulate endometriosis pathogenesis and immune response
Authors: Lingegowda Harshavardhan , Zutautas Katherine B , Wei Yuhong , Yolmo Priyanka , Sisnett Danielle J , McCallion Alison , Koti Madhuri , Tayade Chandrakant
Published: April 2024

Endometriosis (EM), characterized by the presence of endometrial-like tissue outside the uterus, is the leading cause of chronic pelvic pain and infertility in females of reproductive age. Despite its high prevalence, the molecular mechanisms underlying EM pathogenesis remain poorly understood. The endocannabinoid system (ECS) is known to influence several cardinal features of this complex disease including pain, vascularization, and overall lesion survival, but the exact mechanisms are not known. Utilizing CNR1 knockout (k/o), CNR2 k/o and wild type (WT) mouse models of EM, we reveal contributions of ECS and these receptors in disease initiation, progression, and immune modulation. Particularly, we identified EM-specific T cell dysfunction in the CNR2 k/o mouse model of EM. We also demonstrate the impact of decidualization-induced changes on ECS components, and the unique disease-associated transcriptional landscape of ECS components in EM. Imaging Mass Cytometry (IMC) analysis revealed distinct features of the microenvironment between CNR1, CNR2, and WT genotypes in the presence or absence of decidualization. This study, for the first time provides an in-depth analysis of the involvement of the ECS in EM pathogenesis and lays the foundation for the development of novel therapeutic interventions to alleviate the burden of this debilitating condition.
Saccharomyces cerevisiae Rev7 promotes non-homologous end-joining by blocking Mre11 nuclease and Rad50’s ATPase activities and homologous recombination
Authors: Badugu Sugith , Dhyani Kshitiza Mohan , Thakur Manoj , Muniyappa Kalappa
Published: April 2024

Recent studies have shown that, in human cancer cells, the tetrameric Shieldin complex (comprising REV7, SHLD1, SHLD2, and SHLD3) facilitates non-homologous end-joining (NHEJ) while blocking homologous recombination (HR). Surprisingly, several eukaryotic species lack SHLD1, SHLD2, and SHLD3 orthologs, suggesting that Rev7 may leverage an alternative mechanism to regulate the double-strand break (DSB) repair pathway choice. Exploring this hypothesis, we discovered that Saccharomyces cerevisiae Rev7 physically interacts with the Mre11–Rad50–Xrs2 (MRX) subunits, impedes G-quadruplex DNA synergized HU-induced toxicity, and facilitates NHEJ, while antagonizing HR. Notably, we reveal that a 42-amino acid C-terminal fragment of Rev7 binds to the subunits of MRX complex, protects rev7∆ cells from G-quadruplex DNA-HU-induced toxicity, and promotes NHEJ by blocking HR. By comparison, the N-terminal HORMA domain, a conserved protein–protein interaction module, was dispensable. We further show that the full-length Rev7 impedes Mre11 nuclease and Rad50’s ATPase activities without affecting the latter’s ATP-binding ability. Combined, these results provide unanticipated insights into the functional interaction between the MRX subunits and Rev7 and highlight a previously unrecognized mechanism by which Rev7 facilitates DSB repair via NHEJ, and attenuation of HR, by blocking Mre11 nuclease and Rad50’s ATPase activities in S. cerevisiae.
Uncovering hidden genetic risk factors for breast and ovarian cancers in BRCA-negative women: a machine learning approach in the Saudi population
Authors: Alganmi Nofe , Bashanfar Arwa , Alotaibi Reem , Banjar Haneen , Karim Sajjad , Mirza Zeenat , Abusamra Heba , Al-Attas Manal , Turkistany Shereen , Abuzenadah Adel
Published: April 2024

Breast and ovarian cancers are prevalent worldwide, with genetic factors such as BRCA1 and BRCA2 mutations playing a significant role. However, not all patients carry these mutations, making it challenging to identify risk factors. Researchers have turned to whole exome sequencing (WES) as a tool to identify genetic risk factors in BRCA-negative women. WES allows the sequencing of all protein-coding regions of an individual’s genome, providing a comprehensive analysis that surpasses traditional gene-by-gene sequencing methods. This technology offers efficiency, cost-effectiveness and the potential to identify new genetic variants contributing to the susceptibility to the diseases. Interpreting WES data for disease-causing variants is challenging due to its complex nature. Machine learning techniques can uncover hidden genetic-variant patterns associated with cancer susceptibility. In this study, we used the extreme gradient boosting (XGBoost) and random forest (RF) algorithms to identify BRCA-related cancer high-risk genes specifically in the Saudi population. The experimental results exposed that the RF method scored superior performance with an accuracy of 88.16% and an area under the receiver-operator characteristic curve of 0.95. Using bioinformatics analysis tools, we explored the top features of the high-accuracy machine learning model that we built to enhance our knowledge of genetic interactions and find complex genetic patterns connected to the development of BRCA-related cancers. We were able to identify the significance of HLA gene variations in these WES datasets for BRCA-related patients. We find that immune response mechanisms play a major role in the development of BRCA-related cancer. It specifically highlights genes associated with antigen processing and presentation, such as HLA-B, HLA-A and HLA-DRB1 and their possible effects on tumour progression and immune evasion. In summary, by utilizing machine learning approaches, we have the potential to aid in the development of precision medicine approaches for early detection and personalized treatment strategies.
Semi or fully automatic tooth segmentation in CBCT images: a review
Authors: Zheng Qianhan , Gao Yu , Zhou Mengqi , Li Huimin , Lin Jiaqi , Zhang Weifang , Chen Xuepeng
Published: April 2024

Cone beam computed tomography (CBCT) is widely employed in modern dentistry, and tooth segmentation constitutes an integral part of the digital workflow based on these imaging data. Previous methodologies rely heavily on manual segmentation and are time-consuming and labor-intensive in clinical practice. Recently, with advancements in computer vision technology, scholars have conducted in-depth research, proposing various fast and accurate tooth segmentation methods. In this review, we review 55 articles in this field and discuss the effectiveness, advantages, and disadvantages of each approach. In addition to simple classification and discussion, this review aims to reveal how tooth segmentation methods can be improved by the application and refinement of existing image segmentation algorithms to solve problems such as irregular morphology and fuzzy boundaries of teeth. It is assumed that with the optimization of these methods, manual operation will be reduced, and greater accuracy and robustness in tooth segmentation will be achieved. Finally, we highlight the challenges that still exist in this field and provide prospects for future directions.
Magnification in preclinical procedures: effect on muscle activity and angular deviations of the neck and trunk
Authors: Pazos Júlia Margato , Fernandes Ana Flávia Ribeiro Monteiro , Verri Edson Donizetti , Gomes Guilherme Gallo Costa , Regalo Simone Cecílio Hallak , Garcia Patricia Petromilli Nordi Sasso
Published: April 2024

Objectives

This study aimed to assess the effects of different magnification systems on the angular deviations of the neck and trunk and the muscle activities of the upper back and neck during preclinical cavity preparation.

Methods

This was an experimental laboratory study, with the angular deviations from the neutral positions of the neck and trunk and the activities of the bilateral upper back (the descending and ascending trapezius) and neck (sternocleidomastoid) muscles as the dependent variables. The independent variables were the different magnification systems used (Simple, Galilean, and Keplerian loupes, with direct vision as the control) and prepared teeth (teeth 16, 26, 36, and 46). A dental mannequin phantom head with artificial resin teeth was used, and Class I cavity preparations for composite resin were performed on teeth 16, 26, 36, and 46 using a 1012 round diamond bur at low speed. To analyze the angular deviations, the postures adopted during the procedure were recorded using a tripod-mounted camera positioned to provide a lateral view of the operator. A trained researcher measured the angular deviations using the software entitled “Software for Postural Assessment”—SAPO (version 0.69). Bilateral muscle activity was assessed using surface electromyography. Descriptive statistical analysis was performed, and after verifying the assumptions of normality and homoscedasticity, two-way analysis of variance and the Tukey and Games-Howell post-hoc tests were used to compare the data (α=0.05).

Results

The angular deviation from the neutral position of the neck was found to be significantly higher during cavity preparations performed with the naked eye and the Simple loupe, irrespective of the prepared tooth. With regard to tooth location, the angular deviation of the neck was significantly greater during cavity preparation on teeth 16 and 26, and the angular deviation of the trunk was significantly greater during cavity preparation on tooth 26, regardless of the magnification system used. There were significant differences in right sternocleidomastoid muscle activity between the Simple, Galilean, and Keplerian loupes, with activity being the lowest for the Galilean loupe (p = 0.008). There were no significant differences in left sternocleidomastoid muscle activity between the loupes, regardless of the prepared tooth (p = 0.077). The activities of the bilateral descending trapezius and the right ascending trapezius muscles were significantly lower when the Galilean loupe was used (p < 0.010).

Conclusion

These results suggest that the Galilean loupe resulted in lower muscle activity in the neck and back regions and that the Galilean and Keplerian loupes resulted in less angular deviations of the neck and trunk during cavity preparation.
Discovery and validation of molecular patterns and immune characteristics in the peripheral blood of ischemic stroke patients
Authors: Cong Lin , He Yijie , Wu Yun , Li Ze , Ding Siwen , Liang Weiwei , Xiao Xingjun , Zhang Huixue , Wang Lihua
Published: April 2024

Background

Stroke is a disease with high morbidity, disability, and mortality. Immune factors play a crucial role in the occurrence of ischemic stroke (IS), but their exact mechanism is not clear. This study aims to identify possible immunological mechanisms by recognizing immune-related biomarkers and evaluating the infiltration pattern of immune cells.

Methods

We downloaded datasets of IS patients from GEO, applied R language to discover differentially expressed genes, and elucidated their biological functions using GO, KEGG analysis, and GSEA analysis. The hub genes were then obtained using two machine learning algorithms (least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE)) and the immune cell infiltration pattern was revealed by CIBERSORT. Gene-drug target networks and mRNA-miRNA-lncRNA regulatory networks were constructed using Cytoscape. Finally, we used RT-qPCR to validate the hub genes and applied logistic regression methods to build diagnostic models validated with ROC curves.

Results

We screened 188 differentially expressed genes whose functional analysis was enriched to multiple immune-related pathways. Six hub genes (ANTXR2, BAZ2B, C5AR1, PDK4, PPIH, and STK3) were identified using LASSO and SVM-RFE. ANTXR2, BAZ2B, C5AR1, PDK4, and STK3 were positively correlated with neutrophils and gamma delta T cells, and negatively correlated with T follicular helper cells and CD8, while PPIH showed the exact opposite trend. Immune infiltration indicated increased activity of monocytes, macrophages M0, neutrophils, and mast cells, and decreased infiltration of T follicular helper cells and CD8 in the IS group. The ceRNA network consisted of 306 miRNA-mRNA interacting pairs and 285 miRNA-lncRNA interacting pairs. RT-qPCR results indicated that the expression levels of BAZ2B, C5AR1, PDK4, and STK3 were significantly increased in patients with IS. Finally, we developed a diagnostic model based on these four genes. The AUC value of the model was verified to be 0.999 in the training set and 0.940 in the validation set.

Conclusion

Our research explored the immune-related gene expression modules and provided a specific basis for further study of immunomodulatory therapy of IS.
Unveiling the aesthetic secrets: exploring connections between genetic makeup, chemical, and environmental factors for enhancing/improving the color and fragrance/aroma of Chimonanthus praecox
Authors: Zhao Haoyu , Masood Hafiza Ayesha , Muhammad Sher
Published: April 2024

Floral color and scent profiles vary across species, geographical locations, and developmental stages. The exclusive floral color and fragrance of Chimonanthus praecox is contributed by a range of endogenous chemicals that distinguish it from other flowers and present amazing ornamental value. This comprehensive review explores the intricate interplay of environmental factors, chemicals and genes shaping the flower color and fragrance of Chimonanthus praecox. Genetic and physiological factors control morpho-anatomical attributes as well as pigment synthesis, while environmental factors such as temperature, light intensity, and soil composition influence flower characteristics. Specific genes control pigment synthesis, and environmental factors such as temperature, light intensity, and soil composition influence flower characteristics. Physiological processes including plant hormone contribute to flower color and fragrance. Hormones, notably ethylene, exert a profound influence on varioustraits. Pigment investigations have spotlighted specific flavonoids, including kaempferol 3-O-rutinoside, quercetin, and rutin. Red tepals exhibit unique composition with cyanidin-3-O-rutinoside and cyanidin-3-O-glucoside being distinctive components. Elucidating the molecular basis of tepal color variation, particularly in red and yellow varieties, involves the identification of crucial regulatory genes. In conclusion, this review unravels the mysteries of Chimonanthus praecox, providing a holistic understanding of its flower color and fragrance for landscape applications. This comprehensive review uniquely explores the genetic intricacies, chemical and environmental influences that govern the mesmerizing flower color and fragrance of Chimonanthus praecox, providing valuable insights for its landscape applications. This review article is designed for a diverse audience, including plant geneticists, horticulturists, environmental scientists, urban planners, and students, offering understandings into the genetic intricacies, ecological significance, and practical applications of Chimonanthus praecox across various disciplines. Its appeal extends to professionals and enthusiasts interested in plant biology, conservation, and industries dependent on unique floral characteristics.