Combinations of deletion and missense variations of the dynein-2 DYNC2LI1 subunit found in skeletal ciliopathies cause ciliary defects

Cilia play crucial roles in sensing and transducing extracellular signals. Bidirectional protein trafficking within cilia is mediated by the intraflagellar transport (IFT) machinery containing IFT-A and IFT-B complexes, with the aid of kinesin-2 and dynein-2 motors. The dynein-2 complex drives retrograde trafficking of the IFT machinery after its transportation to the ciliary tip as an IFT cargo. Mutations in genes encoding the dynein-2-specific subunits (DYNC2H1, WDR60, WDR34, DYNC2LI1, and TCTEX1D2) are known to cause skeletal ciliopathies. We here demonstrate that several pathogenic variants of DYNC2LI1 are compromised regarding their ability to interact with DYNC2H1 and WDR60. When expressed in DYNC2LI1-knockout cells, deletion variants of DYNC2LI1 were unable to rescue the ciliary defects of these cells, whereas missense variants, as well as wild-type DYNC2LI1, restored the normal phenotype. DYNC2LI1-knockout cells coexpressing one pathogenic deletion variant together with wild-type DYNC2LI1 demonstrated a normal phenotype. In striking contrast, DYNC2LI1-knockout cells coexpressing the deletion variant in combination with a missense variant, which mimics the situation of cells of compound heterozygous ciliopathy individuals, demonstrated ciliary defects. Thus, DYNC2LI1 deletion variants found in individuals with skeletal ciliopathies cause ciliary defects when combined with a missense variant, which expressed on its own does not cause substantial defects.

Types of constitutional diatheses in children with tuberculosis infection

Diathesis or constitutional abnormality is a polygenically inherited tendency of an organism to diseases, objectively recognized by deviations from the normal phenotype. There are 4 types of diatheses: exudative-catarrhal, lymphatic-hypoplastic, neuro-arthritic and allergic. The aim of the work was to identify and determine the frequency of diathesis in children with different course of tuberculosis infection. 225 children aged from 1 to 14 years were examined: 108 children with active forms of tuberculosis; 54 children with residual post-tuberculosis changes; 63 children with latent tuberculosis infection. It was found that among patients with active tuberculosis, children with lymphatic-hypoplastic (17.6 ± 3.7%) and neuro-arthritic diathesis (16.7 ± 3.6%) are most common, and children with allergic diathesis (11.1 ± 3.0% of cases) are less common. Children with lymphatic-hypoplastic diathesis often develop a complicated course of tuberculosis (26.3 ± 10.1%), there is a pronounced intoxication syndrome (58.0± 11.3%). The frequency of occurrence of children with allergic diathesis is higher in patients with residual post-tuberculosis changes (29.6 ± 6.2%) and with latent tuberculosis infection (33.3 ± 6.0%) than in patients with active tuberculosis (11.1 ± 3.0%).

Simple morphometrics for predicting lordosis-induced deviations of body-shape in reared Gilthead seabream (Sparus aurata L.)

Haemal lordosis, V-shape bending of the haemal vertebrae, is a frequent abnormality of reared fish. Lordosis severity ranges from light deformations of vertebral axis, with insignificant effects on external morphology, to severe axis deformations with significant impact on body-shape. In the present study, we developed a simple morphometric index (PrAn) that links lordosis severity at the juvenile stage with fish body-shape at harvesting, without requiring to radiograph or sacrifice the samples. Examined seabream specimens were part of our previous study (Fragkoulis et al. 2019, Sci. Rep. 9, 9832), which monitored the effects of lordosis on the external morphology of pit-tagged seabream juveniles during their growth, up to harvest size. At both juvenile and adult stages, PrAn was effective in discriminating the normal fish from ca the 70% of lordotic fish. Our results suggest the PrAn as a valuable scale of quality, which quantifies the lordosis effects on fish external morphology, both at the juvenile stage and at harvest. Depending on the lordosis rates, and the hatchery strategy on the maximum allowed abnormality rates, this scale can cull out different rates of lordotic fish, without affecting the fish with normal phenotype or the lordotic fish with high recovery potential.

Sequential development of embryoblast memory entities in human cancer tissues, architectural metamorphosis from spiral cleavage to micro – macroscopic structures

ABSTRACTEvery cancer cell can partially or completely return to an embryonic genotype-phenotype: We were able to capture the evolutionary cycle of the activation of an individual cellular memory, which allowed a group of squamous tumor cells with mutations caused by the Human Papilloma Virus to return collectively to an embryoid-like state, in unique images. Somatic cells have the plasticity to transform their morphology into an embryonic phenotype when they enter a state of cellular emergency.Our findings document how malignant tissues reactivated ancestral storage memory and elaborate, high-fidelity crystalline fractal chiral structures (Tc) repaired copies from damaged substrate tissue. Harnessing this resultant perfect embryoblast memory template probably guides and controls the regenerative pathway mechanism in human tissues as follows: a) Modify and reprogram the phenotype of the tumor where these entities are generated. b) Establish a reverse primordial microscopic mold to use the collective behavior of cellular building blocks to regenerate injured tissues. c) Convert cancer cells to a normal phenotype by developmental patterning of active patterning cues. d) Convert cancer cells to a normal phenotype by regeneration using the organizational level and scale properties of reverse genetic guidance. e) Globally control mitotic activity and morphogenetic movements, preventing its spread and metastasis, determining a better prognosis for patients who incubate these entities in their tumors compared to those who do not express them. f) Under physical-chemical cellular stress it is possible to artificially replicate these entities from the epithelium of minor salivary glands in humans.

Ergatandromorphism in the Ant Myrmica lobulicornis Nylander, 1857 (Formicidae: Myrmicinae)

Ergatandromorphism is the result of an aberrant development in which part of the body of a social insect shows the traits of the worker caste, while the other resembles a male. It is considered a specific case of gynandromorphism. Specimens with these characteristics have rarely been collected in different ant lineages across the world. Here, we provide the first description of ergatandromorphism in the ant Myrmica lobulicornis Nylander, 1857: an ergatandromorphous specimen was recovered during an arthropod sampling campaign across altitudinal and ecological gradients on the Italian Alps (Stelvio National Park), together with 480 workers and 4 queens of the same species, which expressed the normal phenotype.

Effect of witches’ broom mutation on growth of Pinus sibirica seedlings

Mutational witches’ brooms (WB) spontaneously arise in the tree crown. There are no male cones in Pinus sibirica WB and pollination always occurs with normal pollen. We studied 2-year-old seed progeny obtained from open-pollinated cones of WB and normal crown (NC) pines. There were significant morphological differences in two pairs of WB and NC families, while the third family pair studied showed barely pronounced differences. Segregation analysis of WB seed progeny based on needle length (growth trait) and total bud number (branching trait) revealed that about half of seedlings had a normal phenotype, while mutants were from 15.6 to 35.7 %. The rest seedlings could not be unambiguously identified, because they have not yet fully demonstrated the phenotype. Looking normal seedlings from WB families differed not only from mutants but also from NC progeny. Therefore, the mutation had some effect on both mutant seedlings and seedlings with a normal phenotype. Moreover, the denser was maternal WB the more differences were observed between WB and NC progeny.

Immunophenotype Drift of Residual Plasma Cells Indicates Therapeutic Response and Prognosis in Multiple Myeloma

Background Chemotherapy resistance remains a significant hurdle in the treatment of multiple myeloma (MM). However, it is difficult to discriminate the potential refractory patients from the very early stage. Flow cytometry is a convenient tool to detect the residual myeloma cell tiding, indicating therapeutic response sensitively. Methods From June, 2014 to December, 2016, 172 sequential patients with newly diagnosed multiple myeloma were enrolled in the BDH2008/02 clinical trial. Patient informed consent was obtained in accordance with the Declaration of Helsinki. 144 patients with at least two flow cytometry detections were analyzed. Bone marrow samples were detected by an eight-color EuroFlow panel. CD20 negative and CD81 positive is defined as normal phenotype. Results We conducted a median of 3-time (2-8) flow cytometry detection on each patient. When newly diagnosed and achieved best response, CD20, CD81 expression rates were 29.9%, 9.7% and 14.9%, 64.4% (P=0.0091, P<0.0001), respectively. According to the status variation of CD20 and CD81, all patients were divided into three groups: both markers were always normal (Group A), either CD20 or CD81 was abnormal at diagnosed and turned normal during therapy (Group B) and markers stayed abnormal (Group C). Patients with undetectable residual tumor cells were also classified as Group A. The overall response rate of the patients in Group C was inferior to Group B (>PR rate: 54.3% vs. 71.4%, P=0.021). And the OS of Group C was significantly worse than Group A and B (47.9 months vs. not reached vs. not reached, P=0.036). Conclusion CD20/CD81 switching to normal phenotype during therapy indicates therapeutic response and an improved outcome than that staying abnormal. The expression tiding of CD20 and CD81 may be a reasonable combination to dynamically stratify MM patients, directing the choice of maintenance therapy. Figure Disclosures No relevant conflicts of interest to declare.