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1.
Int J Mol Sci ; 25(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-39000272

ABSTRACT

In recent years, interest in very small proteins (µ-proteins) has increased significantly, and they were found to fulfill important functions in all prokaryotic and eukaryotic species. The halophilic archaeon Haloferax volcanii encodes about 400 µ-proteins of less than 70 amino acids, 49 of which contain at least two C(P)XCG motifs and are, thus, predicted zinc finger proteins. The determination of the NMR solution structure of HVO_2753 revealed that only one of two predicted zinc fingers actually bound zinc, while a second one was metal-free. Therefore, the aim of the current study was the homologous production of additional C(P)XCG proteins and the quantification of their zinc content. Attempts to produce 31 proteins failed, underscoring the particular difficulties of working with µ-proteins. In total, 14 proteins could be produced and purified, and the zinc content was determined. Only nine proteins complexed zinc, while five proteins were zinc-free. Three of the latter could be analyzed using ESI-MS and were found to contain another metal, most likely cobalt or nickel. Therefore, at least in haloarchaea, the variability of predicted C(P)XCG zinc finger motifs is higher than anticipated, and they can be metal-free, bind zinc, or bind another metal. Notably, AlphaFold2 cannot correctly predict whether or not the four cysteines have the tetrahedral configuration that is a prerequisite for metal binding.


Subject(s)
Archaeal Proteins , Haloferax volcanii , Zinc Fingers , Zinc , Haloferax volcanii/metabolism , Haloferax volcanii/chemistry , Zinc/metabolism , Zinc/chemistry , Archaeal Proteins/chemistry , Archaeal Proteins/metabolism , Protein Binding , Amino Acid Sequence
2.
Sensors (Basel) ; 24(13)2024 Jun 24.
Article in English | MEDLINE | ID: mdl-39000879

ABSTRACT

Competitive climbers engage in highly structured training regimens to achieve peak performance levels, with efficient time management as a critical aspect. Neuromuscular electrical stimulation (NMES) training can close the gap between time-efficient conditioning training and achieving optimal prerequisites for peak climbing-specific performances. Therefore, we examined potential neuromuscular adaptations resulting from the NMFES intervention by analyzing the efficacy of twice-weekly NMES-supported fingerboard (hang board) training compared with thrice-weekly conventional fingerboard training over 7 training weeks in enhancing climbing-specific endurance among intermediate to advanced climbers. Participants were randomly divided into the NMES and control groups. Eighteen participants completed the study (14 male, 4 female; mean age: 25.7 ± 5.3 years; mean climbing experience: 6.4 ± 3.4 years). Endurance was assessed by measuring the maximal time athletes could support their body weight (hanging to exhaustion) on a 20 mm-deep ledge at three intervals: pre-, in-between- (after 4 weeks of training), and post-training (after 7 weeks of training). The findings revealed that despite the lower training volume in the NMES group, no significant differences were observed between the NMES and control groups in climbing-specific endurance. Both groups exhibited notable improvements in endurance, particularly after the in-between test. Consequently, a twice-weekly NMES-supported fingerboard training regimen demonstrated non-inferiority to a thrice-weekly conventional training routine. Incorporating NMES into fingerboard workouts could offer time-saving benefits.


Subject(s)
Electric Stimulation , Fingers , Physical Endurance , Humans , Male , Female , Adult , Physical Endurance/physiology , Fingers/physiology , Electric Stimulation/methods , Young Adult , Athletes , Mountaineering/physiology
3.
Cureus ; 16(5): e61250, 2024 May.
Article in English | MEDLINE | ID: mdl-38947663

ABSTRACT

A 59-year-old woman, who previously underwent surgery on her left long finger A1 pulley and left small finger distal interphalangeal joint for triggering and mallet deformity at another medical facility in March 2021, sought evaluation at an Orthopedics Hand clinic. She presented with limited finger movement, a flexion contracture, and difficulty extending her left long finger. Examination revealed an A2 pulley injury with extensive scar tissue. Subsequently, she underwent surgery to remove the scar tissue and reconstruct the A2 pulley using suture tape anchors. This case highlights the negative outcome following A1 pulley release due to an unintended A2 injury, resulting in significant scarring and an intrinsic plus digit posture. Additionally, it underscores the potential effectiveness of using non-absorbable synthetic sutures to minimize scarring and promote an early range of motion in cases where healing leads to excessive scarring around the flexor tendon sheath.

4.
Trauma Case Rep ; 52: 101052, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38948102

ABSTRACT

Thumb distal amputation refers to the loss of a portion of the thumb at or near the tip, which can be caused by various injuries such as crush injuries, lacerations, or avulsions. Several surgical methods can be used to repair thumb distal amputations, including composite graft, flap reconstruction, replantation, and amputation revision. In this case report, we describe a successful surgical procedure performed on three healthy men (19, 26, and 44 years old) who suffered a sharp amputation of their left and right hands thumb. In one case initial fixation of the amputated part was performed by a general orthopedic surgeon as a composite graft, two other cases were referred us without any procedure. The procedure involved irrigation and minimal debridement and deepithelializing the amputated part and fixation it with one or two 1.5 mm steinman pins and repairing the nail bed with7/0 absorbable sutures. An adiposofaciocutaneous flap from the index finger was used to cover the pulp of the thumb and the nail bed, while a full-thickness grafts from the same wrist in one case and medial part of ipsilateral arm in others were used to repair the defect on the dorsal side of the index finger. The wound was dressed, and the sutures were removed after two weeks. The base of the flap was detached from the index finger after three weeks, and the kwires were removed after six weeks. The flap and graft were successfully taken, except for a small part of the tip of the thumb. Two years after the operation, in two patients and 3 months in whom was operated recently, all the patient's thumbs had a reasonable shape and length with minimal nail deformity. The use of an index finger based adiposofaciocutaneous flap and full-thickness graft in these cases allowed for successful reconstruction of the thumb and, improving both function and appearance.

5.
Exp Ther Med ; 28(2): 334, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39011065

ABSTRACT

Numerous studies have reported the potential involvement of ferroptosis in the development of atherosclerosis (AS). Acyl-CoA synthetase long chain family member 4 (ACSL4) is an essential component in the promotion of ferroptosis. The present study aimed to investigate the role of ACSL4 and zinc finger translocation-associated protein (ZFTA) in the regulation of endothelial cell ferroptosis in AS. Human umbilical vein endothelial cells (HUVECs) with ACSL4 knockout were generated using CRISPR/Cas9 technology. To assess ferroptosis, malondialdehyde concentration, iron content and reactive oxygen species levels were quantified in the present study. In addition, western blot analysis was conducted to explore the potential mechanisms underlying ACSL4 and ZFTA in the modulation of ferroptosis in HUVECs. The results of the present study demonstrated that the expression levels of ACSL4 and ZFTA were significantly increased in human atherosclerotic plaques. In addition, ACSL4 knockout led to a reduced susceptibility to ferroptosis, while ZFTA contributed to ferroptosis in HUVECs. Results of the present study also demonstrated that ZFTA overexpression upregulated ACSL4 expression in HUVECs, whereas ZFTA knockdown led to decreased ACSL4 expression. Co-transfection experiments demonstrated that the ZTFA overexpression-mediated increase in ferroptosis was reversed following ACSL4 knockdown. Collectively, results of the present study highlighted that ACSL4 mediated the effects of ZFTA on the ferroptosis of HUVECs. Thus, the present study demonstrated the potential role of ACSL4 and ZFTA in the regulation of ferroptosis, and highlighted that ferroptosis-related pathways may act as potential targets in the treatment of AS.

6.
Methods Mol Biol ; 2842: 3-20, 2024.
Article in English | MEDLINE | ID: mdl-39012588

ABSTRACT

The introduction of CRISPR/Cas systems has resulted in a strong impulse for the field of gene-targeted epigenome/epigenetic reprogramming (EpiEditing), where EpiEditors consisting of a DNA binding part for targeting and an enzymatic part for rewriting of chromatin modifications are applied in cells to alter chromatin modifications at targeted genome loci in a directed manner. Pioneering studies preceding this era indicated causal relationships of chromatin marks instructing gene expression. The accumulating evidence of chromatin reprogramming of a given genomic locus resulting in gene expression changes opened the field for mainstream applications of this technology in basic and clinical research. The growing knowledge on chromatin biology and application of EpiEditing tools, however, also revealed a lack of predictability of the efficiency of EpiEditing in some cases. In this perspective, the dependence of critical parameters such as specificity, effectivity, and sustainability of EpiEditing on experimental settings and conditions including the expression levels and expression times of the EpiEditors, their chromatin binding affinity and specificity, and the crosstalk between EpiEditors and cellular epigenome modifiers are discussed. These considerations highlight the intimate connection between the outcome of epigenome reprogramming and the details of the technical approaches toward EpiEditing, which are the main topic of this volume of Methods in Molecular Biology. Once established in a fully functional "plug-and-play" mode, EpiEditing will allow to better understand gene expression control and to translate such knowledge into therapeutic tools. These expectations are beginning to be met as shown by various in vivo EpiEditing applications published in recent years, several companies aiming to exploit the therapeutic power of EpiEditing and the first clinical trial initiated.


Subject(s)
CRISPR-Cas Systems , Chromatin , Epigenesis, Genetic , Epigenome , Gene Editing , Humans , Gene Editing/methods , Chromatin/genetics , Chromatin/metabolism , Animals , Epigenomics/methods
7.
Methods Mol Biol ; 2842: 23-55, 2024.
Article in English | MEDLINE | ID: mdl-39012589

ABSTRACT

The advent of locus-specific protein recruitment technologies has enabled a new class of studies in chromatin biology. Epigenome editors (EEs) enable biochemical modifications of chromatin at almost any specific endogenous locus. Their locus-specificity unlocks unique information including the functional roles of distinct modifications at specific genomic loci. Given the growing interest in using these tools for biological and translational studies, there are many specific design considerations depending on the scientific question or clinical need. Here, we present and discuss important design considerations and challenges regarding the biochemical and locus specificities of epigenome editors. These include how to: account for the complex biochemical diversity of chromatin; control for potential interdependency of epigenome editors and their resultant modifications; avoid sequestration effects; quantify the locus specificity of epigenome editors; and improve locus-specificity by considering concentration, affinity, avidity, and sequestration effects.


Subject(s)
Chromatin , Gene Editing , Humans , Chromatin/genetics , Chromatin/metabolism , Gene Editing/methods , Epigenome , Epigenomics/methods , Epigenesis, Genetic , Genetic Loci , Animals , CRISPR-Cas Systems
8.
Protein Expr Purif ; 222: 106542, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38969281

ABSTRACT

Human ZC3H11A is an RNA-binding zinc finger protein involved in mRNA export and required for the efficient growth of human nuclear replicating viruses. Its biochemical properties are largely unknown so our goal has been to produce the protein in a pure and stable form suitable for its characterization. This has been challenging since the protein is large (810 amino acids) and with only the N-terminal zinc finger domain (amino acids 1-86) being well structured, the remainder is intrinsically disordered. Our production strategies have encompassed recombinant expression of full-length, truncated and mutated ZC3H11A variants with varying purification tags and fusion proteins in several expression systems, with or without co-expression of chaperones and putative interaction partners. A range of purification schemes have been explored. Initially, only truncated ZC3H11A encompassing the zinc finger domain could successfully be produced in a stable form. It required recombinant expression in insect cells since expression in E. coli gave a protein that aggregated. To reduce problematic nucleic acid contaminations, Cys8, located in one of the zinc fingers, was substituted by Ala and Ser. Interestingly, this did not affect nucleic acid binding, but the full-length protein was stabilised while the truncated version was insoluble. Ultimately, we discovered that when using alkaline buffers (pH 9) for purification, full-length ZC3H11A expressed in Sf9 insect cells was obtained in a stable and >90 % pure form, and as a mixture of monomers, dimers, tetramers and hexamers. Many of the challenges experienced are consistent with its predicted structure and unusual charge distribution.


Subject(s)
Escherichia coli , RNA-Binding Proteins , Humans , RNA-Binding Proteins/genetics , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/isolation & purification , Escherichia coli/genetics , Escherichia coli/metabolism , Animals , Zinc Fingers , Recombinant Proteins/genetics , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Recombinant Proteins/biosynthesis , Recombinant Proteins/metabolism , Sf9 Cells , Protein Stability , Intrinsically Disordered Proteins/genetics , Intrinsically Disordered Proteins/chemistry , Intrinsically Disordered Proteins/isolation & purification , Intrinsically Disordered Proteins/metabolism , Intrinsically Disordered Proteins/biosynthesis
9.
Elife ; 132024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995818

ABSTRACT

Members of the diverse heterochromatin protein 1 (HP1) family play crucial roles in heterochromatin formation and maintenance. Despite the similar affinities of their chromodomains for di- and tri-methylated histone H3 lysine 9 (H3K9me2/3), different HP1 proteins exhibit distinct chromatin-binding patterns, likely due to interactions with various specificity factors. Previously, we showed that the chromatin-binding pattern of the HP1 protein Rhino, a crucial factor of the Drosophila PIWI-interacting RNA (piRNA) pathway, is largely defined by a DNA sequence-specific C2H2 zinc finger protein named Kipferl (Baumgartner et al., 2022). Here, we elucidate the molecular basis of the interaction between Rhino and its guidance factor Kipferl. Through phylogenetic analyses, structure prediction, and in vivo genetics, we identify a single amino acid change within Rhino's chromodomain, G31D, that does not affect H3K9me2/3 binding but disrupts the interaction between Rhino and Kipferl. Flies carrying the rhinoG31D mutation phenocopy kipferl mutant flies, with Rhino redistributing from piRNA clusters to satellite repeats, causing pronounced changes in the ovarian piRNA profile of rhinoG31D flies. Thus, Rhino's chromodomain functions as a dual-specificity module, facilitating interactions with both a histone mark and a DNA-binding protein.


Subject(s)
Chromatin , Chromobox Protein Homolog 5 , Chromosomal Proteins, Non-Histone , Drosophila Proteins , Drosophila melanogaster , Animals , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Chromosomal Proteins, Non-Histone/metabolism , Chromosomal Proteins, Non-Histone/genetics , Chromatin/metabolism , Chromatin/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Evolution, Molecular , Phylogeny , Protein Binding , RNA, Small Interfering/metabolism , RNA, Small Interfering/genetics , Histones/metabolism , Histones/genetics , DNA/metabolism , DNA/genetics
10.
Oncol Lett ; 28(2): 392, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38966585

ABSTRACT

The AT-rich interacting domain-containing protein 1A (ARID1A) is a tumor suppressor gene that has been implicated in several cancers, including colorectal cancer (CRC). The present study used a proteomic approach to elucidate the molecular mechanisms of ARID1A in CRC carcinogenesis. Stable ARID1A-overexpressing SW48 colon cancer cells were established using lentivirus transduction and the successful overexpression of ARID1A was confirmed by western blotting. Label-free quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry identified 705 differentially altered proteins in the ARID1A-overexpressing cells, with 310 proteins significantly increased and 395 significantly decreased compared with empty vector control cells. Gene Ontology enrichment analysis highlighted the involvement of the altered proteins mainly in the Wnt signaling pathway. Western blotting supported these findings, as a decreased protein expression of Wnt target genes, including c-Myc, transcription factor T cell factor-1/7 and cyclin D1, were observed in ARID1A-overexpressing cells. Among the altered proteins involved in the Wnt signaling pathway, the interaction network analysis revealed that ARID1A exhibited a direct interaction with E3 ubiquitin-protein ligase zinc and ring finger 3 (ZNRF3), a negative regulator of the Wnt signaling pathway. Further analyses using the The Cancer Genome Atlas colon adenocarcinoma public dataset revealed that ZNRF3 expression significantly impacted the overall survival of patients with CRC and was positively correlated with ARID1A expression. Finally, an increased level of ZNRF3 in ARID1A-overexpressing cells was confirmed by western blotting. In conclusion, the findings of the present study suggest that ARID1A negatively regulates the Wnt signaling pathway through ZNRF3, which may contribute to CRC carcinogenesis.

11.
Ophthalmologie ; 2024 Jul 02.
Article in German | MEDLINE | ID: mdl-38953924

ABSTRACT

CLINICAL FEATURES: The click phenomenon occurs when an acquired mechanical restriction of the elevation in adduction of the eye or of the extension of the finger/thumb, is forcefully overcome. The common cause is a nodule either of the superior oblique tendon posterior to the trochlea in the case of a Jaensch-Brown syndrome or of the digital flexor tendon anterior to the A1 annular pulley in the case of a trigger finger. Both locations share similar anatomical conditions for the development of the nodule and the pathomechanism of the click. RESULTS: From these identical findings in the eye and the hand in small children it can be assumed that the results from the studies of the hand in newborns and infants with a trigger thumb/finger are also applicable to the situation of the eye. 1. This motility disorder is not congenital. This is most likely due to an incomplete development at the time of birth of the sliding factors needed for a free passage of the tendon through the trochlea and the A1 annular pulley. 2. A distinction must be made between stages 0-3: stage 0 = no more restriction of the motility and no click phenomenon; stage 1 = forced active extension/elevation possible; stage 2 = only passive extension/elevation, each with a click phenomenon; stage 3 = no extension/elevation possible and no click phenomenon. 3. In most cases in early childhood there is a spontaneous complete recovery (75% after 6-7 years). In the eye this spontaneous course can only limitedly be shortened with motility exercises in combination with segmental occlusion. CONCLUSION: The click phenomenon is a symptom of stages 1 and 2 of an acquired mechanical restriction of the elevation in adduction of the eye or the extension of the finger/thumb. It should not be called a syndrome.

12.
Int Orthop ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953949

ABSTRACT

PURPOSE: Trigger finger (TF) is a common hand condition that can be treated with surgery. We conducted a systematic review and meta-analysis to assess whether ultrasound-guided (US-guided) percutaneous surgery is superior to other conventional surgical methods. METHODS: We conducted a comprehensive search in Medline, Embase, and the Cochrane Library to identify relevant studies. We included randomized clinical trials (RCTs) and observational studies comparing US-guided TF release with blind percutaneous or open approaches. We combined Risk Ratios (RR) and Mean Differences (MD) with 95% Confidence Intervals (CI) across studies. Data processing and analysis were conducted using R software, version 4.3.1. RESULTS: Our analysis included eight RCTs and two observational studies with 555 patients. US-guided surgery significantly reduced postoperative DASH scores (MD -3.75 points; 95% CI = -7.48, -0.02; p < 0.01), shortened time to resume activities (MD -11.52 days; 95% CI = -16.13, -6.91; p < 0.01), hastened discontinuation of oral analgesics (MD -4.44 days; 95% CI = -8.01, -0.87; p < 0.01), and improved patient satisfaction scores (RR 1.13; 95% CI = 1.04, 1.23; p = 0.75). There were no significant differences in VAS scores, time to movement recovery, or surgical success rate. CONCLUSION: Ultrasound-guided percutaneous release is a safe, effective, and superior alternative for treating TF compared to other methods, leading to improved DASH scores, quicker recovery, faster cessation of oral analgesics, and enhanced patient satisfaction.

13.
Adv Protein Chem Struct Biol ; 141: 255-297, 2024.
Article in English | MEDLINE | ID: mdl-38960477

ABSTRACT

Glial cells provide physical and chemical support and protection for neurons and for the extracellular compartments of neural tissue through secretion of soluble factors, insoluble scaffolds, and vesicles. Additionally, glial cells have regenerative capacity by remodeling their physical microenvironment and changing physiological properties of diverse cell types in their proximity. Various types of aberrant glial and macrophage cells are associated with human diseases, disorders, and malignancy. We previously demonstrated that transmembrane protein, TMEM230 has tissue revascularization and regenerating capacity by its ability to secrete pro-angiogenic factors and metalloproteinases, inducing endothelial cell sprouting and channel formation. In healthy normal neural tissue, TMEM230 is predominantly expressed in glial and marcophate cells, suggesting a prominent role in neural tissue homeostasis. TMEM230 regulation of the endomembrane system was supported by co-expression with RNASET2 (lysosome, mitochondria, and vesicles) and STEAP family members (Golgi complex). Intracellular trafficking and extracellular secretion of glial cellular components are associated with endocytosis, exocytosis and phagocytosis mediated by motor proteins. Trafficked components include metalloproteins, metalloproteinases, glycans, and glycoconjugate processing and digesting enzymes that function in phagosomes and vesicles to regulate normal neural tissue microenvironment, homeostasis, stress response, and repair following neural tissue injury or degeneration. Aberrantly high sustained levels TMEM230 promotes metalloprotein expression, trafficking and secretion which contribute to tumor associated infiltration and hypervascularization of high tumor grade gliomas. Following injury of the central nervous or peripheral systems, transcient regulated upregulation of TMEM230 promotes tissue wound healing, remodeling and revascularization by activating glial and macrophage generated microchannels/microtubules (referred to as vascular mimicry) and blood vessel sprouting and branching. Our results support that TMEM230 may act as a master regulator of motor protein mediated trafficking and compartmentalization of a large class of metalloproteins in gliomas and gliosis.


Subject(s)
Glioma , Gliosis , Membrane Proteins , Humans , Membrane Proteins/metabolism , Glioma/metabolism , Glioma/pathology , Gliosis/metabolism , Gliosis/pathology , Animals , Receptors, Peptide
14.
J Comp Neurol ; 532(7): e25648, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38958676

ABSTRACT

In this study, we investigated recurrent copy number variations (CNVs) in the 19p12 locus, which are associated with neurodevelopmental disorders. The two genes in this locus, ZNF675 and ZNF681, arose via gene duplication in primates, and their presence in several pathological CNVs in the human population suggests that either or both of these genes are required for normal human brain development. ZNF675 and ZNF681 are members of the Krüppel-associated box zinc finger (KZNF) protein family, a class of transcriptional repressors important for epigenetic silencing of specific genomic regions. About 170 primate-specific KZNFs are present in the human genome. Although KZNFs are primarily associated with repressing retrotransposon-derived DNA, evidence is emerging that they can be co-opted for other gene regulatory processes. We show that genetic deletion of ZNF675 causes developmental defects in cortical organoids, and our data suggest that part of the observed neurodevelopmental phenotype is mediated by a gene regulatory role of ZNF675 on the promoter of the neurodevelopmental gene Hes family BHLH transcription factor 1 (HES1). We also find evidence for the recently evolved regulation of genes involved in neurological disorders, microcephalin 1 and sestrin 3. We show that ZNF675 interferes with HES1 auto-inhibition, a process essential for the maintenance of neural progenitors. As a striking example of how some KZNFs have integrated into preexisting gene expression networks, these findings suggest the emergence of ZNF675 has caused a change in the balance of HES1 autoregulation. The association of ZNF675 CNV with human developmental disorders and ZNF675-mediated regulation of neurodevelopmental genes suggests that it evolved into an important factor for human brain development.


Subject(s)
Primates , Transcription Factor HES-1 , Humans , Animals , Transcription Factor HES-1/genetics , Transcription Factor HES-1/metabolism , Primates/genetics , Homeostasis/physiology , Homeostasis/genetics , DNA Copy Number Variations/genetics , Mice , Biological Evolution , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism
15.
J Leukoc Biol ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38970506

ABSTRACT

In the era of personalized cancer treatment, understanding the complexities of tumor biology and immune modulation is paramount. This comprehensive analysis delves into the multifaceted role of Zinc Finger Protein 207 (ZNF207) in pan-cancer, shedding light on its involvement in tumorigenesis, immune evasion, and therapeutic implications. Through integrated genomic and clinical data analysis, we reveal consistent upregulation of ZNF207 across diverse cancer types, highlighting its potential as a prognostic marker and therapeutic target, particularly for liver cancers. Notably, ZNF207 demonstrates intricate associations with clinical-pathological features, immune subtypes, and molecular pathways, indicating its pervasive influence in cancer biology. Furthermore, our study uncovers ZNF207's involvement in immune escape mechanisms, suggesting its potential as a modulator of immune responses within the tumor microenvironment. These findings underscore the significance of ZNF207 in shaping cancer progression and immune landscape, presenting promising avenues for targeted therapy and immunomodulation. Recognizing ZNF207's multifaceted contributions to cancer progression and immune evasion suggests its central role in understanding tumor immunology, beyond mere therapeutic targeting. Nevertheless, further mechanistic studies are imperative to elucidate ZNF207's precise molecular mechanisms and therapeutic implications in cancer treatment. This study primarily utilized various bioinformatics tools such as TIMER 2.0, cProSite, UALCAN, SangerBox, GEPIA2, TISIDB and TIDE to analyze the expression of ZNF207 in multiple cancer samples from the TCGA database.

16.
Neurophysiol Clin ; 54(5): 102985, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970865

ABSTRACT

OBJECTIVE: This study aimed to explore the relationships between potential neurophysiological biomarkers and upper limb motor function recovery in stroke patients, specifically focusing on combining two neurophysiological markers: electroencephalography (EEG) and transcranial magnetic stimulation (TMS). METHODS: This cross-sectional study analyzed neurophysiological, clinical, and demographical data from 102 stroke patients from the DEFINE cohort. We searched for correlations of EEG and TMS measurements combined to build a prediction model for upper limb motor functionality, assessed by five outcomes, across five assessments: Fugl-Meyer Assessment (FMA), Handgrip Strength Test (HST), Finger Tapping Test (FTT), Nine-Hole Peg Test (9HPT), and Pinch Strength Test (PST). RESULTS: Our multivariate models agreed on a specific neural signature: higher EEG Theta/Alpha ratio in the frontal region of the lesioned hemisphere is associated with poorer motor outcomes, while increased MEP amplitude in the non-lesioned hemisphere correlates with improved motor function. These relationships are held across all five motor assessments, suggesting the potential of these neurophysiological measures as recovery biomarkers. CONCLUSION: Our findings indicate a potential neural signature of brain compensation in which lower frequencies of EEG power are increased in the lesioned hemisphere, and lower corticospinal excitability is also increased in the non-lesioned hemisphere. We discuss the meaning of these findings in the context of motor recovery in stroke.

17.
Exp Brain Res ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992203

ABSTRACT

We explored two types of anticipatory synergy adjustments (ASA) during accurate four-finger total force production task. The first type is a change in the index of force-stabilizing synergy during a steady state when a person is expecting a signal to produce a quick force change, which is seen even when the signal does not come (steady-state ASA). The other type is the drop in in the synergy index prior to a planned force change starting at a known time (transient ASA). The subjects performed a task of steady force production at 10% of maximal voluntary contraction (MVC) followed by a ramp to 20% MVC over 1 s, 3 s, and as a step function (0 s). In another task, in 50% of the trials during the steady-state phase, an unexpected signal could come requiring a quick force pulse to 20% MVC (0-surprise). Inter-trial variance in the finger force space was used to quantify the index of force-stabilizing synergy within the uncontrolled manifold hypothesis. We observed significantly lower synergy index values during the steady state in the 0-ramp trials compared to the 1-ramp and 3-ramp trials. There was also larger transient ASA during the 0-ramp trials. In the 0-surprise condition, the synergy index was significantly higher compared to the 0-ramp condition whereas the transient ASA was significantly larger. The finding of transient ASA scaling is of importance for clinical studies, which commonly involve populations with slower actions, which can by itself be associated with smaller ASAs. The participants varied the sharing pattern of total force across the fingers more in the task with "surprises". This was coupled to more attention to precision of performance, i.e., inter-trial deviations from the target as reflected in smaller variance affecting total force, possibly reflecting higher concentration on the task, which the participants perceived as more challenging compared to a similar task without surprise targets.

18.
Adv Rheumatol ; 64(1): 53, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992697

ABSTRACT

Trigger finger (TF) is a disorder characterized by snapping or locking a finger. It has a prevalence of greater than 3% in the general population; however, this estimate could be increased to 5% up to 20% in diabetic patients. Some unreal ambiguity about definition, pathophysiology, site of lesion, and etiology are found among researchers and clinicians, leading to a lack of understanding of all aspects of the disease and improper management as many clinicians proceed to anti-inflammatory medications or steroids injection without in-depth patient evaluation. Original articles cited up to 2022, found through a Google search using the specified keywords, have been used in this review. Close-access articles were accessed through our researcher account with the Egyptian Knowledge Bank. In this review, we will focus on pathophysiology to present all possible findings and etiology to represent all risk factors and associated diseases to assess and confirm a diagnosis and the exact location of pathology hence better treatment modalities and reducing the recurrence of the pathology.


Subject(s)
Trigger Finger Disorder , Humans , Trigger Finger Disorder/etiology , Trigger Finger Disorder/physiopathology , Risk Factors
19.
Sci Rep ; 14(1): 15972, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987302

ABSTRACT

Task-specific dystonia leads to loss of sensorimotor control for a particular motor skill. Although focal in nature, it is hugely disabling and can terminate professional careers in musicians. Biomarkers for underlying mechanism and severity are much needed. In this study, we designed a keyboard device that measured the forces generated at all fingertips during individual finger presses. By reliably quantifying overflow to other fingers in the instructed (enslaving) and contralateral hand (mirroring) we explored whether this task could differentiate between musicians with and without dystonia. 20 right-handed professional musicians (11 with dystonia) generated isometric flexion forces with the instructed finger to match 25%, 50% or 75% of maximal voluntary contraction for that finger. Enslaving was estimated as a linear slope of the forces applied across all instructed/uninstructed finger combinations. Musicians with dystonia had a small but robust loss of finger dexterity. There was increased enslaving and mirroring, primarily during use of the symptomatic hand (enslaving p = 0.003; mirroring p = 0.016), and to a lesser extent with the asymptomatic hand (enslaving p = 0.052; mirroring p = 0.062). Increased enslaving and mirroring were seen across all combinations of finger pairs. In addition, enslaving was exaggerated across symptomatic fingers when more than one finger was clinically affected. Task-specific dystonia therefore appears to express along a gradient, most severe in the affected skill with subtle and general motor control dysfunction in the background. Recognition of this provides a more nuanced understanding of the sensorimotor control deficits at play and can inform therapeutic options for this highly disabling disorder.


Subject(s)
Dystonic Disorders , Fingers , Motor Skills , Music , Humans , Fingers/physiopathology , Fingers/physiology , Male , Adult , Female , Dystonic Disorders/physiopathology , Motor Skills/physiology , Middle Aged , Young Adult
20.
Heliyon ; 10(12): e32774, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38975087

ABSTRACT

Finger millet, an important 'Nutri-Cereal' and climate-resilient crop, is cultivated as a marginal crop in calcareous soils. Calcareous soils have low organic carbon content, high pH levels, and poor structure. Such a situation leads to poor productivity of the crop. Site-specific nutrient management (SSNM), which focuses on supplying optimum nutrients when a crop is needed, can ensure optimum production and improve the nutrient and energy use efficiency of crops. Moreover, developing an appropriate SSNM technique for this crop could offer new insights into nutrient management practices, particularly for calcareous soils. A field experiment was conducted during the rainy seasons of 2020 and 2021 in calcareous soil at Dr. Rajendra Prasad Central Agricultural University, Pusa, India. The experiment consisted of 8 treatments, viz. control, nitrogen (N)/phosphorus (P)/potassium (K)-omission, 75 %, 100 %, and 125 % recommended fertilizer dose (RFD), and 100 % recommended P and K + 30 kg ha-1 N as basal + rest N as per GreenSeeker readings. From this study, it was observed that the GreenSeeker-based SSNM resulted in the maximum grain yield (2873 kg ha-1), net output energy (96.3 GJ ha-1), and agronomic efficiency of N (30.6 kg kg-1), P (68.9 kg kg-1), and K (68.9 kg kg-1). The application of 125 % RFD resulted in ∼7 % lower yield than that under GreenSeeker-based nutrient management. Approximately 12 % greater energy use efficiency and 21-36 % greater nutrient use efficiency were recorded under GreenSeeker-based nutrient management than under 125 % RDF. The indigenous supplies of N, P, and K were found to be 14.31, 3.00, and 18.51 kg ha-1, respectively. Thus, 100 % of the recommended P and K + 30 kg ha-1 N as basal + rest N according to GreenSeeker readings can improve the yield, nutrient use efficiency, and energy balance of finger millet in calcareous soils.

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