CRL

Pathomechanisms that activate oncogenic B-cell receptor (BCR) signaling in diffuse large B-cell lymphoma (DLBCL), are largely unknown. Kelch-like family member 6 (KLHL6) encoding a substrate-adapter for Cullin-3-RING E3 ubiquitin-ligase (CRL) with poorly established targets is recurrently mutated in DLBCL. By applying high-throughput protein interactome screens and functional characterization, we discovered that KLHL6 regulates BCR by targeting its signaling subunits CD79A and CD79B. Loss of physiological KLHL6 expression pattern was frequent among the MCD/C5-like activated B-cell DLBCLs and was associated with higher CD79B levels and dismal outcome...

Cullin RING E3 ligases (CRL) have emerged as key regulators of disease-modifying pathways and therapeutic targets. Cullin3 (Cul3)-containing CRL (CRL3) has been implicated in regulating hepatic insulin and oxidative stress signaling. However, CRL3 function in liver pathophysiology is poorly defined. Here, we report that hepatocyte Cul3 knockout results in rapid resolution of steatosis in obese mice. However, the remarkable resistance of hepatocyte Cul3 knockout mice to developing steatosis does not lead to overall metabolic improvement but causes systemic metabolic disturbances...

Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain, engages CUL3 to form the central scaffold of a cullin-RING E3 ligase complex (CRL3KCTD5 ) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3NTD /Gβ1 γ2 assembly reveals a highly dynamic complex with rotations of over 60° between the KCTD5BTB /CUL3NTD and KCTD5CTD /Gβγ moieties of the structure...

Curriculum reinforcement learning (CRL) allows solving complex tasks by generating a tailored sequence of learning tasks, starting from easy ones and subsequently increasing their difficulty. Although the potential of curricula in RL has been clearly shown in various works, it is less clear how to generate them for a given learning environment, resulting in various methods aiming to automate this task. In this work, we focus on framing curricula as interpolations between task distributions, which has previously been shown to be a viable approach to CRL...

BACKGROUND: Gastrointestinal transit (GIT) is influenced by factors including diet, medications, genetics, and gut microbiota, with slow GIT potentially indicating a functional disorder linked to conditions, such as constipation. Although GIT studies have utilized various animal models, few effectively model spontaneous slow GIT. AIMS: We aimed to characterize the GIT phenotype of CFP/Yit (CFP), an inbred mouse strain with suggested slow GIT. METHODS: Female and male CFP mice were compared to Crl:CD1 (ICR) mice in GIT and assessed based on oral gavage of fluorescent-labeled 70-kDa dextran, feed intake, fecal amount, and fecal water content...

The temporal fascia is a double lamina sandwiching a thick fat layer above the zygomatic bony arch. To characterize each lamina, their developmental processes were examined in fetuses. We observed histological sections from 22 half-heads of 10 mid-term fetuses at 14-18 weeks (crown-rump length, 95-150 mm) and 12 near-term fetuses at 26-40 weeks (crown-rump length, 215-334 mm). The superficial lamina of the temporal fascia was not evident at mid-term. Instead, a loose subcutaneous tissue was attached to the thin, deep lamina of the temporal fascia covering the temporalis muscle...

BACKGROUND: Frozen embryo transfer resulted in a higher birthweight and an increased risk of macrosomia than fresh embryo transfer. However, the mechanism was still unclear. When the impact of frozen embryo transfer on fetal growth began was unknown. Crown-rump length at 11-13 weeks had been regarded as a good indicator of fetal growth in the first trimester and had been used for gestational age calculation in women with uncertain last menstrual periods. OBJECTIVE: To evaluate the association between frozen embryo transfer and early fetal growth, particularly the crown-rump length, then fresh embryo transfer...

Calcitriol circulates at low levels in normal human and rodent fetuses, in part due to increased 24-hydroxylation of calcitriol and 25-hydroxyvitamin D by 24-hydroxylase (CYP24A1). Inactivating mutations of CYP24A1 cause high postnatal levels of calcitriol and the human condition of infantile hypercalcemia type 1, but whether the fetus is disturbed by the loss of CYP24A1 is unknown. We hypothesized that loss of Cyp24a1 in fetal mice will cause high calcitriol, hypercalcemia, and increased placental calcium transport...

OBJECTIVE: Immigrant Latinas, particularly of Mexican descent, initially achieve healthy perinatal outcomes. Although this advantage wears off across generations in the United States (US), the early life psychosocial mechanisms that may initiate a cascade of biological vulnerabilities remain elusive. The current investigation aims to understand the extent to which childhood experiences of racism may contribute to elevated levels of C-Reactive Protein (CRP), an early indicator of cardiometabolic risk, during the first postpartum year...

Enzyme immobilization in membrane bioreactors has been considered as a practical approach to enhance the stability, reusability, and efficiency of enzymes. In this particular study, a new type of hybrid membrane reactor was created through the phase inversion method, utilizing hybrid of graphene oxide nanosheets (GON) and polyether sulfone (PES) in order to covalently immobilize the Candida rugosa lipase (CRL). The surface of hybrid membrane was initially modified by (3-Aminopropyl) triethoxysilane (APTES), before the use of glutaraldehyde (GLU), as a linker, through the imine bonds...

INTRODUCTION: Mucins released from epithelial tumors have been proposed to play a role in cancer-associated thrombosis. Mucin1 (MUC1) is a transmembrane mucin that is overexpressed in a variety of human malignancies, including breast and pancreatic cancer. We analyzed the association of MUC1 and venous thrombosis in a mouse tumor model and in patients with cancer. MATERIALS AND METHODS: We used a human pancreatic cancer cell line HPAF-II that expresses a high level of MUC1...

BACKGROUND: Following the first locally transmitted case in Sukhbaatar soum, Selenge Province, we aimed to investigate the ultimate scale of the epidemic in the scenario of uninterrupted transmission. METHODS: This was a prospective case study following the locally modified WHO FFX cases generic protocol. A rapid response team collected data from November 14 to 29, 2020. We created a stochastic process to draw many transmission chains from this greater distribution to better understand and make inferences regarding the outbreak under investigation...

BACKGROUND: The global incidence target for the elimination of hepatitis C among people who inject drugs (PWID) is <2/100. In Norway, the hepatitis C epidemic is concentrated in PWID. Immigrants are the second most important risk group for chronic infection. We modelled the incidence of hepatitis C among active PWID, and the prevalence of chronic infection among active PWID, ex-PWID and immigrants in Norway until 2022. METHODS: We built a stochastic compartmental model, which was informed using data from national data sources, literature, and expert opinion...

High concentrations of low-density particles may cause effects in acute inhalation toxicity studies which can be easily underestimated or misinterpreted following strictly the OECD TG 436, i.e., limited parameters as mortality and gross lesions will be evaluated only. Seven particle types (synthetic amorphous silica (SAS) HMDZ-SAS, silica gel, pyrogenic SAS, and precipitated SAS, calcium carbonate, aluminum oxide pyrogenic alumina, organic red pigment) were chosen at the highest technically feasible concentration of approximately 500mg/m3 for acute inhalation studies with an expanded endpoint setup...

BACKGROUND: Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) globally exhibits a high prevalence and serves as a potential precursor to multidrug-resistant tuberculosis (MDR-TB). Recognizing the spatial distribution of Hr-TB and identifying associated factors can provide strategic entry points for interventions aimed at early detection of Hr-TB and prevention of its progression to MDR-TB. This study aims to analyze spatial patterns and identify socioeconomic, demographic, and healthcare factors associated with Hr-TB in Shanghai at the county level...

The aim of this study was to examine the acute effects of low-intensity one-legged electrical muscle stimulation (EMS) for skeletal muscle on arterial stiffness in EMS and non-EMS legs. Eighteen healthy subjects received two different protocols (Control (CT) and Experimental (ET) trials) in random order on separate days. EMS was applied to the left lower limb at 4 Hz for 20 min at an intensity corresponding to an elevation in pulse rate of approximately 15 beats/min (10.9 ± 5...

STUDY QUESTION: Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles? SUMMARY ANSWER: Using the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles...

STUDY QUESTION: What is the association between first trimester maternal tryptophan (TRP) metabolites and embryonic and fetal growth? SUMMARY ANSWER: Higher 5-hydroxytryptophan (5-HTP) concentrations are associated with reduced embryonic growth and fetal growth and with an increased risk of small-for-gestational age (SGA), while higher kynurenine (KYN) concentrations are associated with a reduced risk of SGA. WHAT IS KNOWN ALREADY: The maternal TRP metabolism is involved in many critical processes for embryonic and fetal growth, including immune modulation and regulation of vascular tone...

BACKGROUND: Knowledge of gestational age (GA) is key in clinical management of individual obstetric patients, and critical to be able to calculate rates of preterm birth and small for GA at a population level. Currently, the gold standard for pregnancy dating is measurement of the fetal crown rump length at 11-14 weeks of gestation. However, this is not possible for women first presenting in later pregnancy, or in settings where routine ultrasound is not available. A reliable, cheap and easy to measure GA-dependent biomarker would provide an important breakthrough in estimating the age of pregnancy...

This study established a Candida rugosa lipase (CRL) system to catalyze triolein and ethyl ferulate interesterification. The products were identified, and the binding mode between the substrates and CRL was predicted through molecular docking. Three methods for preparing CRL-AuNPs were proposed and characterized. It was found that the addition of 40 mL of 15 nm gold nanoparticles increased the CRL activity from 3.05 U/mg to 4.75 U/mg, but the hybridization efficiency was only 32.7 %. By using 4 mL of 0...