Wolbachia in Antarctic terrestrial invertebrates: Absent or undiscovered?

Interactions between a host organism and its associated microbiota, including symbiotic bacteria, play a crucial role in host adaptation to changing environmental conditions. Antarctica provides a unique environment for the establishment and maintenance of symbiotic relationships. One of the most extensively studied symbiotic bacteria in invertebrates is Wolbachia pipientis, which is associated with a wide variety of invertebrates.

Larval morphology of Belgica antarctica Jacobs, 1900 (Diptera, Chironomidae, Orthocladiinae) from central part of the maritime Antarctic and deformities found in the larvae.

The larval morphology of the endemic species Belgica antarctica Jacobs, collected in January and February (2022) from six sites of Antarctica, was studied. The mouth apparatus and the parapods of one hundred seventy-six larvae were analyzed. No differences were found in the morphology of these structures between individuals of different sites.

Pharmacokinetics, pharmacodynamics, and exposure-efficacy of dupilumab in adults with atopic dermatitis.

The pharmacokinetics (PKs) and exposure-efficacy of dupilumab have not been fully described for adults with atopic dermatitis (AD). Our objectives were to analyze the PKs and exposure-efficacy of dupilumab in adults with AD and compare the results of Japanese and overall populations. Adults with moderate-to-severe AD were randomly assigned to dupilumab (300 mg weekly [qw] or every 2 weeks [q2w], 200 mg q2w, 300 mg every 4 weeks [q4w], or 100 mg q4w) or placebo for 16 weeks in a randomized, double-blind, placebo-controlled, dose-ranging phase IIb trial (NCT01859988).

External Morphology of Larvae of Jacobs, 1900 (Diptera, Chironomidae) Obtained from Two Locations in Maritime Antarctica.

The external morphology of the fourth-instar larva of the Antarctic endemic chironomid midge is described. Larvae were collected from Jougla Point (Wiencke Island) and an un-named island close to Enterprise Island, off the coast of the western Antarctic Peninsula. Light microscopy was used to examine and document photographically the structures of the mouthparts (mandible, mentum, premandible, labrum), antennae, pecten epipharyngis, clypeus, frontal apotome and posterior parapods.

The Posology of Dupilumab in Pediatric Patients With Atopic Dermatitis.

Dupilumab demonstrated efficacy with an acceptable safety profile in two randomized, double-blind, placebo-controlled, parallel-group, phase III trials in adolescents (12-17 years; LIBERTY AD ADOL) and children (6-11 years; LIBERTY AD PEDS) with atopic dermatitis (AD) treated for 16 weeks. Here, we present the pharmacokinetic profiles and exposure-response (E-R) relationships of dupilumab that guided the posology in these populations. A total of 251 adolescent patients with moderate-to-severe AD were randomized to subcutaneous dupilumab monotherapy every 2 weeks (q2w; 200 mg q2w, baseline weight < 60 kg; 300 mg q2w, ≥ 60 kg), dupilumab 300 mg every 4 weeks (q4w; non-weight tiered), or placebo; 367 children with severe AD were randomized to dupilumab q2w (100 mg q2w, baseline weight < 30 kg; 200 mg q2w, ≥ 30 kg), dupilumab 300 mg q4w, or placebo.

Base and Covariate Population Pharmacokinetic Analyses of Dupilumab in Adolescents and Children ≥6 to <12 Years of Age Using Phase 3 Data.

Population pharmacokinetic (PK) base and covariate analyses were conducted using data from adolescents with moderate-to-severe atopic dermatitis (AD) and children ≥6 to <12 years of age with severe AD. Two phase 3 studies were analyzed (165 adolescents and 241 children on active treatment). A 2-compartment model with linear and Michaelis-Menten elimination and 3 transit compartments describing lag time in absorption was utilized.

Belgica antarctica (Diptera: Chironomidae): A natural model organism for extreme environments.

Belgica antarctica (Diptera: Chironomidae), a brachypterous midge endemic to the maritime Antarctic, was first described in 1900. Over more than a century of study, a vast amount of information has been compiled on the species (3 750 000 Google search results as of January 10, 2021), encompassing its ecology and biology, life cycle and reproduction, polytene chromosomes, physiology, biochemistry and, increasingly, omics. In 2014, B.

Pharmacokinetics and Pharmacodynamics of Subcutaneous Sarilumab and Intravenous Tocilizumab Following Single-Dose Administration in Patients With Active Rheumatoid Arthritis on Stable Methotrexate.

We assessed pharmacokinetics (PK), pharmacodynamics (PD), and PK/PD relationships of interleukin-6 (IL-6), soluble IL-6 receptor, and C-reactive protein (CRP) in serum, and absolute neutrophil count (ANC) in blood following single doses of subcutaneous sarilumab versus intravenous tocilizumab (NCT02097524) from patients with rheumatoid arthritis (RA) who are inadequate responders to methotrexate (MTX) and on a stable dose of MTX. Patients with RA randomized (1:1:1:1) to single-dose sarilumab (150 or 200 mg subcutaneously) or tocilizumab (4 or 8 mg/kg intravenously) were included (n = 101), and PK, PD, and PK/PD relationships and safety were assessed over 6 weeks postdose. PK profiles for both drugs are described by parallel linear and nonlinear target-mediated clearance pathways.

Population Pharmacodynamic Model of Neutrophil Margination and Tolerance to Describe Effect of Sarilumab on Absolute Neutrophil Count in Patients with Rheumatoid Arthritis.

Evidence suggests that effects of interleukin-6 pathway inhibitors sarilumab, tocilizumab, and sirukumab on absolute neutrophil count (ANC) are due to margination of circulating neutrophils into rapidly mobilizable noncirculating pools. We developed a population pharmacodynamic model using compartments for neutrophil margination and ANC-specific tolerance to describe rapid, transient ANC changes in blood following administration of subcutaneous sarilumab and intravenous/subcutaneous tocilizumab based on data from 322 patients with rheumatoid arthritis in two single-dose (NCT02097524 and NCT02404558) and one multiple-dose (NCT01768572) trials. The model incorporated a tolerance compartment to account for ANC nadir and beginning of recovery before maximal drug concentration after subcutaneous dosing, and absence of a nadir plateau when the ANC response is saturated after subcutaneous or intravenous dosing.

Base and Covariate Population Pharmacokinetic Analyses of Dupilumab Using Phase 3 Data.

Population pharmacokinetic base and covariate models were developed to study functional dupilumab for regulatory submissions, using data from healthy volunteers and patients with moderate-to-severe atopic dermatitis (AD) receiving intravenous or subcutaneous doses. Sixteen studies were pooled (N = 2115; 202 healthy volunteers, 1913 AD patients). The best model was a 2-compartment model with linear and Michaelis-Menten elimination and 3 transit compartments describing absorption.

Vitamin D Signaling Suppresses Early Prostate Carcinogenesis in TgAPT Mice.

We tested whether lifelong modification of vitamin D signaling can alter the progression of early prostate carcinogenesis in studies using mice that develop high-grade prostatic intraepithelial neoplasia that is similar to humans. Two tissue-limited models showed that prostate vitamin D receptor (VDR) loss increased prostate carcinogenesis. In another study, we fed diets with three vitamin D levels (inadequate = 25 IU/kg diet, adequate for bone health = 150 IU/kg, or high = 1,000 IU/kg) and two calcium levels (adequate for bone health = 0.

Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation.

Background/aims: Human enterocytic differentiation is altered during development, fasting, adaptation, and bariatric surgery, but its intracellular control remains unclear. We hypothesized that Schlafen 12 (SLFN12) regulates enterocyte differentiation.

Methods: We used laser capture dissection of epithelium, qRT-PCR, and immunohistochemistry to evaluate SLFN12 expression in biopsies of control and fasting human duodenal mucosa, and viral overexpression and siRNA to trace the SLFN12 pathway in human Caco-2 and HIEC6 intestinal epithelial cells.

Exploratory Population PK Analysis of Dupilumab, a Fully Human Monoclonal Antibody Against IL-4Rα, in Atopic Dermatitis Patients and Normal Volunteers.

An exploratory population pharmacokinetic model for functional dupilumab was developed. Data from healthy volunteers and patients with atopic dermatitis (AD) receiving intravenous or subcutaneous doses were integrated. The data included 197 participants (2,518 measurements of dupilumab in serum) from six phase I and II studies.

Dll4 Blockade in Stromal Cells Mediates Antitumor Effects in Preclinical Models of Ovarian Cancer.

The Notch ligand delta-like 4 (Dll4) has been identified as a promising target in tumor angiogenesis in preclinical studies, and Dll4 inhibitors have recently entered clinical trials for solid tumors, including ovarian cancers. In this study, we report the development of REGN421 (enoticumab), a fully human IgG1 monoclonal antibody that binds human Dll4 with sub-nanomolar affinity and inhibits Notch signaling. Administering REGN421 to immunodeficient mice engineered to express human Dll4 inhibited the growth of several human tumor xenografts in association with the formation of nonfunctional tumor blood vessels.

Schlafen 12 expression modulates prostate cancer cell differentiation.

Background: Schlafen proteins have previously been linked to leukocyte and intestinal epithelial differentiation. We hypothesized that Schlafen 12 (SLFN12) overexpression in human prostate epithelial cells would modulate expression of prostate-specific antigen (PSA) and dipeptidyl peptidase 4 (DPP4), markers of prostatic epithelial differentiation.

Materials And Methods: Differentiation of the human prostate cancer cell lines LNCaP and PC-3 was compared after infection with an adenoviral vector coding for SLFN12 (Ad-SLFN12) or green fluorescent protein (GFP) only expressing virus (control).

Regulation of epithelial differentiation in rat intestine by intraluminal delivery of an adenoviral vector or silencing RNA coding for Schlafen 3.

Although we stimulate enterocytic proliferation to ameliorate short gut syndrome or mucosal atrophy, less effort has been directed at enterocytic differentiation. Schlafen 3 (Slfn3) is a poorly understood protein induced during IEC-6 enterocytic differentiation. We hypothesized that exogenous manipulation of Slfn3 would regulate enterocytic differentiation in vivo.

The correlation between the expression of differentiation markers in rat small intestinal mucosa and the transcript levels of schlafen 3.

Importance: The normal absorptive function and structural maintenance of the intestinal mucosa depend on a constant process of proliferation of enterocytic stem cells followed by progressive differentiation toward a mature phenotype. The mechanisms that govern enterocytic differentiation in the mucosa of the small intestine are poorly understood.

Objective: To determine whether schlafen 3 (but not other schlafen proteins) act in vivo and whether its effects are limited to the small intestine.

[Visual illusions and moving horizon].

Results of psychological "additional investigation" of the crash of Boeing-737, "Aeroflot-Nord" on 14.09.2008 near Perm are presented.

Influence of defunctionalization and mechanical forces on intestinal epithelial wound healing.

The influence on mucosal healing of luminal nutrient flow and the forces it creates are poorly understood. We hypothesized that altered deformation and extracellular pressure mediate, in part, the effects of defunctionalization on mucosal healing. We created patent or partially obstructing defunctionalizing jejunal Roux-en-Y anastomoses in rats to investigate mucosal healing in the absence or presence of luminal nutrient flow and measured luminal pressures to document partial obstruction.

Loss of MLK3 signaling impedes ulcer healing by modulating MAPK signaling in mouse intestinal mucosa.

Mixed-lineage kinase 3 (MLK3) activates multiple MAPK pathways and can initiate apoptosis, proliferation, migration, or differentiation in different cell types. However, whether MLK3 signaling regulates intestinal epithelial cell sheet migration in vivo is not known. We sought to investigate whether MLK3 signaling is important in intestinal mucosal healing and epithelial cell motility in vivo and in vitro.

Changes in morphology and function in small intestinal mucosa after Roux-en-Y surgery in a rat model.

Background: Currently there is no an appropriate model to study intestinal mucosal atrophy in vivo that preserves the nutritional status of the organism.

Materials And Methods: We created a defunctionalized segment of jejunum via a dead-end Roux-en-Y anastomosis in rats. We compared tissue morphometric parameters in the intestinal mucosa of the defunctionalized bowel with that of the mucosa proximal and distal to the anastomosis.

Dietary vitamin D and vitamin D receptor level modulate epithelial cell proliferation and apoptosis in the prostate.

Low vitamin D (VD) status may increase prostate cancer risk but experimental evidence for this relationship is modest. We tested whether low VD status or VD receptor (VDR) deletion influences prostate epithelial cell (PEC) biology using intact mice, castrated mice, or castrated mice treated with testosterone propionate (TP, 2.5 mg/kg BW).

[Peculiarities of research of flying thinking].

New approach to the research of flying thinking is offered. This approach is based on principals of stage-by-stage approach (research of the reflection of every parameter of flight, than its aggregate in figured and conceptual framework), on the usage of the methods of registration of inner and external characteristics of activity of the air staff with the priority of research of content area and mechanisms of flying thinking, typology of content area and mechanisms of flying thinking. This approach is also based on the effectiveness of reflection by means of correlation of the detected figured and conceptual framework with time and correctness of decisions of test flight tasks and with different psychophysiological characteristics.

[About spatial orientation of flying staff in air].

Were learned peculiarities of spatial orientation by altitude of pilots and students in conditions of flying over a sea and on link trainer Yak-40, were educed psychophysiological and psychological mechanisms of perception of altitude. Was effectuated a valuation of existing and possible methods of teaching of effective orientation in air. Was shown, that pilots with different professional rate make faults as well in visual flying as visual detecting of the altitude.