Complement deficiency

In this study, we investigated a deleterious mutation in the β-xylosidase gene, xylA (AkxylA), in Aspergillus luchuensis mut. kawachii IFO 4308 by constructing an AkxylA disruptant and complementation strains of AkxylA and xylA derived from A. luchuensis RIB2604 (AlxylA), which does not harbor the mutation in xylA. Only the AlxylA complementation strain exhibited significantly higher growth and substantial β-xylosidase activity in medium containing xylan, accompanied by an increase in XylA expression...

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by its large heterogeneity in terms of clinical presentation and severity. The pathophysiology of SLE involves an aberrant autoimmune response against various tissues, an excess of apoptotic bodies, and an overproduction of type-I interferon. The genetic contribution to the disease is supported by studies of monozygotic twins, familial clustering, and genome-wide association studies (GWAS) that have identified numerous risk loci...

In calendar year 2023, the United States Food and Drug Administration (US FDA) approved a total of 55 new molecular entities, of which 12 were in the class of therapeutic antibodies. Besides antibody protein drugs, the US FDA also approved another five non-antibody protein drugs, making the broader class of protein drugs about 31% of the total approved drugs. Among the 12 therapeutic antibodies approved by the US FDA, 8 were relatively standard IgG formats, 3 were bivalent, bispecific antibodies and 1 was a trivalent, bispecific antibody...

OBJECTIVE: Treponema denticola has been strongly implicated in the pathogenesis of chronic periodontitis. Previously, we reported that the potential transcriptional regulator TDE_0259 (oxtR1) is upregulated in the bacteriocin ABC transporter gene-deficient mutant. OxtR1 may regulate genes to adapt to environmental conditions during colonization; however, the exact role of the gene in T. denticola has not been reported. Therefore, we investigated its function using an oxtR1-deficient mutant...

Low level expression in Escherichia coli of the RecA protein from the radiation resistant bacterium Deinococcus radiodurans protects a RecA deficient strain of E. coli from UV-A irradiation by up to ∼160% over basal UV-A resistance. The protection effect is inverse protein dose dependent: increasing the expression level of the D. radiodurans RecA (DrRecA) protein decreases the protection factor. This inverse protein dose dependence effect helps resolve previously conflicting reports of whether DrRecA expression is protective or toxic for E...

BACKGROUND: Unsupervised robot-assisted rehabilitation is a promising approach to increase the dose of therapy after stroke, which may help promote sensorimotor recovery without requiring significant additional resources and manpower. However, the unsupervised use of robotic technologies is not yet a standard, as rehabilitation robots often show low usability or are considered unsafe to be used by patients independently. In this paper we explore the feasibility of unsupervised therapy with an upper limb rehabilitation robot in a clinical setting, evaluate the effect on the overall therapy dose, and assess user experience during unsupervised use of the robot and its usability...

To go beyond the deficiencies of the three conventional multimodal fusion strategies (i.e., input-, feature- and output-level fusion), we propose a bidirectional attention-aware fluid pyramid feature integrated fusion network (BAF-Net) with cross-modal interactions for multimodal medical image diagnosis and prognosis.
Approach: BAF-Net is composed of two identical branches to preserve the unimodal features and one bidirectional attention-aware distillation stream to progressively assimilate cross-modal complements and to learn supplementary features in both bottom-up and top-down processes...

The function of ascorbate peroxidase-related (APX-R) proteins, present in all green photosynthetic eukaryotes, remains unclear. This study focuses on APX-R from Chlamydomonas reinhardtii, namely, ascorbate peroxidase 2 (APX2). We showed that apx2 mutants exhibited a faster oxidation of the photosystem I primary electron donor, P700, upon sudden light increase and a slower re-reduction rate compared to the wild type, pointing to a limitation of plastocyanin. Spectroscopic, proteomic and immunoblot analyses confirmed that the phenotype was a result of lower levels of plastocyanin in the apx2 mutants...

BACKGROUNDDiagnosis of PMM2-CDG, the most common congenital disorder of glycosylation (CDG), relies on measuring carbohydrate-deficient transferrin (CDT) and genetic testing. CDT tests have false negatives and may normalize with age. Site-specific changes in protein N-glycosylation have not been reported in sera in PMM2-CDG.METHODSUsing multistep mass spectrometry-based N-glycoproteomics, we analyzed sera from 72 individuals to discover and validate glycopeptide alterations. We performed comprehensive tandem mass tag-based discovery experiments in well-characterized patients and controls...

INTRODUCTION: Lupus is a diverse autoimmune disease with autoantibody formation. Lupus nephritis carries a grave prognosis. Complement involvement, namely, C1q deficiency, is linked to activity and renal involvement and could help in their assessment. LN therapies include plasma exchange, immune adsorption, and probably hemodiafiltration with online endogenous reinfusion (HFR), together with traditional immunosuppressive therapies. AIM: The aim of this study was to evaluate the role of HFR in improving signs and symptoms of systemic lupus erythematosus (SLE) activity and laboratory parameters in cases not responding to traditional immunosuppressive therapy...

BACKGROUND: Growth hormone deficiency(GHD) and idiopathic short stature(ISS) are the primary causes of short stature in children. Animal experiments have revealed a link between growth hormone(GH), gut microbiota and metabolism, however, limited information is available from human trials. METHODS: Fecal samples collected from GHD (n = 36), ISS (n = 32) and healthy control (HC) children(n = 16) were subjected to microbiome (16 S rRNA gene sequencing) and metabolome (nuclear magnetic resonance,NMR) analyses...

Provider bias based on age, marital status, and parity may be a barrier to quality contraceptive care. However, the extent to which bias leads to disparities in care quality is not well understood. In this mixed-methods study, we used four different data sources from the same facilities to assess the extent of bias and how much it affects contraceptive care. First, we surveyed providers in Tanzania and Burkina Faso (N = 295) to assess provider attitudes about young, unmarried, and nulliparous clients...

UNLABELLED: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations focally develop in multiple organs. These can be small (telangiectasias) or large (arteriovenous malformations, AVMs) and may rupture leading to frequent, uncontrolled bleeding. There are few treatment options and no cure for HHT. Most HHT patients are heterozygous for loss-of-function mutations for Endoglin (ENG) or Alk1 (ACVRL1), however, why loss of these genes manifests as vascular malformations remains poorly understood...

BACKGROUND: Repeated neonatal sevoflurane exposures led to neurocognitive disorders in young mice. We aimed to assess the role of microglia and complement C1q in sevoflurane-induced neurotoxicity and explore the underlying mechanisms. METHODS: Neonatal mice were treated with sevoflurane on postnatal days 6, 8, and 10, and the Morris water maze was performed to assess cognitive functions. For mechanistic explorations, mice were treated with minocycline, C1q-antibody ANX005, and sialidase-inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA) before sevoflurane exposures...

OBJECTIVE: To provide a clinical approach towards immune checkpoint inhibitor (ICI)-associated endocrinopathies, their link with cancer outcomes, factors which differentiate them from other immune related adverse events (irAEs), and health systems innovation to improve care for these patients. METHODS: A literature search for articles pertaining to ICIs and endocrinopathies was performed and supplemented by expert opinions of the authors. RESULTS: While irAEs can affect almost any organ, they frequently target the endocrine glands, most commonly thyroid...

Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group...

Stress-induced fetal programming diminishes β2 adrenergic tone, which coincides with intrauterine growth restriction ( IUGR ) and lifelong metabolic dysfunction. We determined if stimulating β2 adrenergic activity in IUGR-born lambs would improve metabolic outcomes. IUGR lambs that received daily injections of saline or the β2 agonist clenbuterol from birth to 60 days were compared with controls from pair-fed thermoneutral pregnancies. As juveniles, IUGR lambs exhibited systemic inflammation and robust metabolic dysfunction, including greater ( p < 0...

The supramolecular striatin-interacting phosphatases and kinases (STRIPAK) complex is highly conserved in eukaryotes and controls diverse developmental processes in fungi. STRIPAK is genetically and physically linked to the Hippo-related septation initiation network (SIN), which signals through a chain of three kinases, including the terminal nuclear Dbf2-related (NDR) family kinase DBF2. Here, we provide evidence for the function of DBF2 during sexual development and vegetative growth of the homothallic ascomycetous model fungus Sordaria macrospora ...

Computational rhinology is a specialized branch of biomechanics leveraging engineering techniques for mathematical modelling and simulation to complement the medical field of rhinology. Computational rhinology has already contributed significantly to advancing our understanding of the nasal function, including airflow patterns, mucosal cooling, particle deposition, and drug delivery, and is foreseen as a crucial element in, e.g., the development of virtual surgery as a clinical, patient-specific decision support tool...

Hydroxylated (hetero)arenes are valued in many industries as both key constituents of end products and diversifiable synthetic building blocks. Accordingly, the development of reactions that complement and address the limitations of existing methods for the introduction of aromatic hydroxyl groups is an important goal. To this end, we apply base-catalyzed halogen transfer (X-transfer) to enable the direct C-H hydroxylation of mildly acidic N -heteroarenes and benzenes. This protocol employs an alkoxide base to catalyze X-transfer from sacrificial 2-halothiophene oxidants to aryl substrates, forming SN Ar-active intermediates that undergo nucleophilic hydroxylation...