Complete Loss Research Articles

Epidemiology of alopecia areata and population-wide comorbidities in Germany: analysis of longitudinal claimsdata.

Alopecia areata (AA) is a chronic, immune-mediated disease characterized by acute-onset hair loss. The hair loss can range from small, circumscribed hairless areas on the scalp to complete loss of hair on the head and body hair. However, data on the epidemiology of AA are limited. Current evaluations are lacking in Germany. The aim of this study was to evaluate the epidemiology and comorbidity of AA in Germany based on claims data. A representative 40% sample of all adults who were insured with a German statutory health insurance company (DAK-Gesundheit) between 2016 and 2020 was evaluated (n = 2.88 million). Based on at least one relevant outpatient or inpatient diagnosis of International Classification of Diseases (ICD)-10 L63, the annual AA prevalence and incidence (ICD-10 L63) were calculated for 2016 to 2020. Different case definitions were used for diagnosis validation. In addition, the occurrence of comorbidities in patients with AA was investigated. In 2020, AA prevalence was 210 cases per 100 000 and incidence 72 cases per 100 000. Compared with persons without AA, those with AA significantly more often had atopic dermatitis [rate ratio (RR) 2.9], pruritus (RR 2.7), lupus erythematosus (RR 2.4), urticaria (RR2.3) and psoriasis (RR 2.2). Women were affected slightly more often than men (0.2% vs. 0.1%). On a regional level, higher prevalence and incidence rates were found in Brandenburg (prevalence 332 cases per 100 000; incidence 116 cases per 100 000), Hesse (prevalence 344cases per 100 000; incidence 124 cases per 100 000) and Mecklenburg-Western Pomerania (prevalence 303 cases per 100 000; incidence 111per100 000). AA is a common immune-mediated skin condition with marked regional variations in Germany. For a complete understanding of epidemiology, complementary population-based studies including clinical characteristics of AA are useful.

The heparin-binding hemagglutinin protein of Mycobacterium tuberculosis is a nucleoid-associated protein

Nucleoid-associated proteins (NAPs) regulate multiple cellular processes such as gene expression, virulence, and dormancy throughout bacterial species. NAPs help in the survival and adaptation of Mycobacterium tuberculosis (Mtb) within the host. Fourteen NAPs have been identified in Escherichia coli; however, only seven NAPs are documented in Mtb. Given its complex lifestyle, it is reasonable to assume that Mtb would encode for more NAPs. Using bioinformatics tools and biochemical experiments, we have identified the heparin-binding hemagglutinin (HbhA) protein of Mtb as a novel sequence-independent DNA-binding protein which has previously been characterized as an adhesion molecule required for extrapulmonary dissemination. Deleting the carboxy-terminal domain of HbhA resulted in a complete loss of its DNA-binding activity. Atomic force microscopy showed HbhA-mediated architectural modulations in the DNA, which may play a regulatory role in transcription and genome organization. Our results showed that HbhA colocalizes with the nucleoid region of Mtb. Transcriptomics analyses of a hbhA KO strain revealed that it regulates the expression of ∼36% of total and ∼29% of essential genes. Deletion of hbhA resulted in the upregulation of ∼73% of all differentially expressed genes, belonging to multiple pathways suggesting it to be a global repressor. The results show that HbhA is a nonessential NAP regulating gene expression globally and acting as a plausible transcriptional repressor.

IP3R1 underlies diastolic ANO1 activation and pressure-dependent chronotropy in lymphatic collecting vessels.

Pressure-dependent chronotropy of murine lymphatic collecting vessels relies on the activation of the Ca2+-activated chloride channel encoded by Anoctamin 1 (Ano1) in lymphatic muscle cells. Genetic ablation or pharmacological inhibition of ANO1 results in a significant reduction in basal contraction frequency and essentially complete loss of pressure-dependent frequency modulation by decreasing the rate of the diastolic depolarization phase of the ionic pacemaker in lymphatic muscle cells (LMCs). Oscillating Ca2+ release from sarcoendoplasmic reticulum Ca2+ channels has been hypothesized to drive ANO1 activity during diastole, but the source of Ca2+ for ANO1 activation in smooth muscle remains unclear. Here, we investigated the role of the inositol triphosphate receptor 1 (Itpr1; Ip3r1) in this process using pressure myography, Ca2+ imaging, and membrane potential recordings in LMCs of ex vivo pressurized inguinal-axillary lymphatic vessels from control or Myh11CreERT2;Ip3r1fl/fl (Ip3r1ismKO) mice. Ip3r1ismKO vessels had significant reductions in contraction frequency and tone but an increased contraction amplitude. Membrane potential recordings from LMCs of Ip3r1ismKO vessels revealed a depressed diastolic depolarization rate and an elongation of the plateau phase of the action potential (AP). Ca2+ imaging of LMCs using the genetically encoded Ca2+ sensor GCaMP6f demonstrated an elongation of the Ca2+ flash associated with an AP-driven contraction. Critically, diastolic subcellular Ca2+ transients were absent in LMCs of Ip3r1ismKO mice, demonstrating the necessity of IP3R1 activity in controlling ANO1-mediated diastolic depolarization. These findings indicate a critical role for IP3R1 in lymphatic vessel pressure-dependent chronotropy and contractile regulation.

Peroral Endoscopic Myotomy (POEM) and Laparoscopic Heller Myotomy with Dor Fundoplication for Esophagogastric Junction Outflow Obstruction (EGJOO): a Comparison of Outcomes and Impact on Physiology

IntroductionEsophagogastric junction outflow obstruction (EGJOO) is an esophageal motility disorder characterized by failure of lower esophageal sphincter (LES) relaxation with preserved peristalsis. Studies have shown that Heller myotomy with Dor fundoplication (HMD) and per oral endoscopic myotomy (POEM) are effective treatments for EGJOO. However, there is paucity of data comparing the efficacy and impact of these two procedures. Therefore, the aim of this study was to compare outcomes and impact on esophageal physiology in patients undergoing HMD or POEM for primary EGJOO. MethodsThis was a retrospective review of patients who underwent either HMD or POEM for primary EGJOO at our institution between 2013 and 2021. Favorable outcome was defined as an Eckardt score ≤ 3 at 1 year after surgery. GERD–HRQL questionnaire, endoscopy, pH monitoring, and high-resolution manometry (HRM) results at baseline and 1 year after surgery were compared pre- and post-surgery and between groups. Objective GERD was defined as DeMeester score > 14.7 or LA grade C/D esophagitis. ResultsThe final study population consisted of 52 patients who underwent HMD (n = 35) or POEM (n = 17) for EGJOO. At a mean (SD) follow-up of 24.6 (15.3) months, favorable outcome was achieved by 30 (85.7%) patients after HMD and 14 (82.4%) after POEM (p = 0.753). After HMD, there was a decrease GERD-HRQL total score (31 (22–45) to 4 (0–19); p < 0.001), and objective reflux (54.2 to 25.9%; p = 0.033). On manometry, there was a decrease in LES resting pressure (48 (34–59) to 13 (8–17); p < 0.001) and IRP (22 (17–28) to 8 (3–11); p < 0.001), but esophageal body characteristics did not change (p > 0.05). Incomplete bolus clearance improved (70% (10–90) to 10% (0–40); p = 0.010). After POEM, there was no change in the GERD-HRQL total score (p = 0.854), but objective reflux significantly increased (0 to 62%; p < 0.001). On manometry, there was a decrease in LES resting pressure (43 (30–68) to 31 (5–34); p = 0.042) and IRP (23 (18–33) to 12 (10–32); p = 0.048), DCI (1920 (1600–5500) to 0 (0–814); p = 0.035), with increased failed swallows (0% (0–30) to 100% (10–100); p = 0.032). Bolus clearance did not improve (p = 0.539). Compared to HMD, POEM had a longer esophageal myotomy length (11 (7–15)-vs-5 (5–6); p = 0.001), more objective reflux (p = 0.041), lower DCI (0 (0–814)-vs-1695 (929–3101); p = 0.004), and intact swallows (90 (70–100)-vs-0 (0–40); p = 0.006), but more failed swallows (100 (10–100); p = 0.018) and incomplete bolus clearance (90 (90–100)-vs-10 (0–40); p = 0.004). ConclusionPeroral endoscopic myotomy and Heller myotomy with Dor fundoplication are equally effective at relieving EGJOO symptoms. However, POEM causes worse reflux and near complete loss of esophageal body function. Graphical Abstract [Display omitted]

Clinical aspects of the use of a vascularized mucoperiosteal palatine flap for the reconstruction of soft tissue defects

Dental implantation, as a high-tech innovative direction in modern dentistry, can significantly increase the effectiveness of complex rehabilitation of patients with partial and complete loss of teeth. Methods for surgical treatment of patients with soft tissue deficiency in the area of dentition defects must meet the following requirements: minimally invasive; biological feasibility; predictability; the validity of the patterns of changes in the state of soft tissue structures of the maxillofacial during surgical intervention; the need to restore the morphological and functional components of the donor and recipient beds; the most careful attitude to the bone and soft tissue components of the alveolar crest of the jaws for subsequent dental implantation. The article presents the results of a multi-stage method for restoring soft tissue deficiency in 29 patients aged 37 to 60 years with terminal and included defects in the alveolar part of the lower jaw in the distal region using the developed surgical method for eliminating soft tissue deficiency with a vascularized muco-periosteal flap modeled in the projection of the hard palate. The effectiveness of the developed surgical technique is confirmed by clinical data characterizing the intensity of the postoperative inflammatory process, taking into account the developed criteria indicators, as well as morphological indicators of soft tissues in the projection of the apex of the alveolar part of the lower jaw in the area of dentition defects before and 3, 6, 9, 12 months after surgery. It was established that on the 30th day from the moment of surgical manipulations, the intensity of clinical manifestations of the postoperative inflammatory process in the studied patients was completely absent, and by the 12th month, the increase in the thickness of the soft tissue component in the region of the apex of the alveolar part of the lower jaw in the intervention area increased by 133.3%, at the same time, the value of soft tissue growth ranged from 2.2 mm to 3.7 mm. The analysis of the obtained results revealed the high efficiency of the developed method, allowing to expand the indications for dental implantation.

The effect of the combined use of tulatromycin and thymalin in genital mycoplasmosis in cows on cellular immunity indicators

Modern technologies of industrial animal husbandry imply the most effective use of the reproductive potential of females and obtaining healthy young from them. The limiting factor in achieving this goal are diseases characterized by smoothed symptoms, which complicates their timely diagnosis and therapy, one of which is genital mycoplasmosis of cattle. The presence of a long latent period and unclear symptoms allows this disease to remain unnoticed and spread in the herd. During the latent period, morphofunctional changes develop in the body of females, leading to partial or complete loss of reproductive ability. Tetracycline, fluoroquinolone and macrolide antibiotics have been used with varying degrees of effectiveness for the treatment of cows with genital mycoplasmosis, however, antibiotic therapy alone does not restore all functions disrupted during the disease, and in particular does not eliminate immunodeficiency. In this regard, the purpose of our study was to study the inclusion of the immunomodulator thymalin in the treatment regimen of cows with genital mycoplasmosis and its effect on the content of leukocytes, lymphocytes and their subpopulations in the blood. Three groups of animals were formed for the experiment: the first group - pregnant cows with genital mycoplasmosis for the treatment of which the antibiotic traksovet 100 (tulatromycin) was used at a dose of 2.5 mg per 1 kg of animal body weight, subcutaneously, once 40 days before the expected delivery; the second group - pregnant cows with genital mycoplasmosis for the treatment of which the antibiotic traksovet 100 was used at the same dose and the immunomodulator timalin at a dose of 0.1 mg per 1 kg of animal body weight, intramuscularly, twice with an interval of 72 hours; the third group – clinically healthy pregnant cows. In all groups of cows, the number of leukocytes, the percentage of lymphocytes, the absolute and relative content of T-, B- and 0-lymphocytes were determined. It has been established that the use of tulatromycin for the treatment of cows with genital mycoplasmosis gives a good therapeutic effect, but provides only partial restoration of cellular immunity. The combined use of tulatromycin and thymalin has the maximum therapeutic effect and leads to the complete restoration of cellular immunity, and some indicators even slightly exceed their value in clinically healthy cows.

Prevention of sepsis in patients with impaired splenic function

Asplenia refers to the complete loss of spleen function, while hyposplenism refers to the partial loss of splenic function, which may be of primary or secondary origin. The spleen is a secondary lymphoid organ, however, it is also connected with blood circulation. This organ houses a variety of cells, such as T and B lymphocytes, macrophages, dendritic cells, cytokines and antibodies essential for the development of immune responses. In this context, sepsis represents a risk for this group of patients and should be avoided with prophylactic measures, with the majority of infections being caused by encapsulated bacteria. To this end, a literature review was prepared with the main evidence on the prevention of sepsis in patients with asplenia/hyposplenia, using 17 materials from the SciELO, PubMed, Web of Science, Scopus, Cochrane Database of Systematic Reviews (CDSR) databases, EBSCOhost, Virtual Health Library (VHL) and UpToDate. Prevention of sepsis in patients with asplenia or hyposplenia has been shown to involve a combination of vaccination, antibiotic prophylaxis, patient education, and appropriate medical monitoring. It is essential that patients follow medical advice and are aware of the risks and preventive measures necessary to protect their health. Due to the lifelong risk associated with infection in these patients, efforts are focused on improving the quality of care provided to children and adults with restricted splenic function, in addition to ongoing research aimed at alternatives for preventing and treating this condition.

Mutation in Chek2 triggers von Hippel-Lindau hemangioblastoma growth

PurposeVon Hippel-Lindau (VHL) is a rare inherited disease mainly characterized by the growth of tumours, predominantly hemangioblastomas (Hbs) in the CNS and retina, and renal carcinomas. The natural history of VHL disease is variable, differing in the age of onset and its penetrance, even among relatives. Unfortunately, sometimes VHL shows more severe than average: the onset starts in adolescence, and surgeries are required almost every year. In these cases, the factor that triggers the appearance and growth of Hbs usually remains unknown, although additional mutations are suspected.MethodsWe present the case of a VHL patient whose first surgery was at 13 years of age. Then, along his next 8 years, he has undergone 5 surgeries for resection of 10 CNS Hbs. To clarify this severe VHL condition, DNA from a CNS Hb and white blood cells (WBC) was sequenced using next-generation sequencing technology.ResultsMassive DNA sequencing of the WBC (germ line) revealed a pathogenic mutation in CHEK2 and the complete loss of a VHL allele (both tumour suppressors). Moreover, in the tumour sample, several mutations, in BRAF1 and PTPN11 were found. Familiar segregation studies showed that CHEK2 mutation was in the maternal lineage, while VHL was inherited by paternal lineage.ConclusionsFinally, clinical history correlated to the different genotypes in the family, concluding that the severity of these VHL manifestations are due to both, VHL-and-CHEK2 mutations. This case report aims to notice the importance of deeper genetic analyses, in inherited rare diseases, to uncover non-expected mutations.

Broadly potent anti-SARS-CoV-2 antibody shares 93% of epitope with ACE2 and provides full protection in monkeys

Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic monoclonal antibodies, we isolated a potent, broad-spectrum neutralizing antibody that could potentially provide prophylactic protection to immunocompromised patient populations. Spike-specific B-cell clones isolated from a vaccinated post-infected donor were profiled for those producing potent neutralizing antibodies against a panel of SARS-CoV-2 variants. The P4J15 antibody was further characterized to define the structural binding epitope, viral resistance, and in vivo efficacy. The P4J15 mAb shows <20ng/ml neutralizing activity against all variants including the latest XBB.2.3 and EG.5.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares ∼93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. In vitro selection of SARS-CoV-2 mutants escaping P4J15 neutralization showed reduced infectivity, poor ACE2 binding, and mutations are rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, P4J15-LS confers complete prophylactic protection with an exceptionally long in vivo half-life of 43 days. The P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug for prophylactic protection of at-risk patient populations.

Characteristics of speech function in the process of patients getting used to removable dentures

Relevance. The study of the attitude to the disease of dental patients during the adaptation period with the use of conventional clinical research methods is relatively rarely covered in the available domestic and foreign literature. Objective. To study the changes of internal disease pattern after the adaptation period completion in rehabilitation of patients with full tooth loss by full removable acrylic dentures, including the use of such orthopedic dental prosthesis together with the adhesive agent, designed to improve their fixation. Materials and methods. 48 (15 men and 33 women) elderly patients (61–74 years old) with a total loss of teeth were examined and were divided into 2 study groups: 1 – comparison group; 2 – main group. There were also examined 17 elderly people who had no defects of dental rows and formed a control group. The defects of dental rows in the patients of the 1st and 2nd groups were eliminated by making removable dentures. At the same time, during the adaptation period the patients of the second group of the study used a new domestic adhesive cream Aceptа Рarodontal with an extract of medicinal herbs for fixation of dentures. Before treatment and during the adaptation period the types of patients’ relation to the disease were investigated; for this purpose the clinical technique «Type of relation to the disease» (TORD) was usedResults. It was found that while preserving the integrity of dental rows in elderly people the types of attitude to the disease included in the conditionally adaptive block were mainly marked. At the end of adaptation period if all patients of the main group 2 had the types of attitude towards the disease included in the first conditionally adaptive block, then the patients of the comparison group 1 in only 39.1% of people revealed similar types of attitude towards the disease, which testified to the problems in adaptation to new removable acrylic dentures made for the treatment of complete tooth loss. Conclusion. The use of ASEPTA РARODONTAL adhesive cream with herbal extracts by patients provides a positive correction of the internal picture of the disease and the patient’s personal reaction to the treatment. On the basis of the carried out research it is possible to recommend to patients the domestic adhesive cream ASEPTA РARODONTAL for denture fixation in order to optimize the adaptation period to removable acrylic dentures as well as for permanent use, which will improve not only fixation and stabilization of dentures, condition of denture bed mucosa, but also quality of speech function.

Analysis of the Operational and Safety Features of the In-Core Bubbling System of the Molten Salt Fast Reactor

A foreseen feature of the Molten Salt Fast Reactor is the adoption of a bubbling system for the removal of gaseous and metallic fission products (FPs). This mechanism injects helium bubbles into the core to remove FPs from the salt through floating and mass transfer mechanisms for metallic and gaseous FPs, respectively. The present work is aimed at analyzing this helium bubbling system, focusing on gaseous FPs. We investigate both operational and safety-related features in order to get information useful for the design and to assess the convenience of its adoption. Accordingly, our investigations split into two strands: (1) analyzing the characteristics of the bubbling system itself and (2) assessing the safety features of the reactor in its presence. In order to perform the above analyses, we add the capability to simulate production, transport, and mass transfer of an arbitrary number of gaseous FPs to a preexisting multiphysics solver, built with the OpenFOAM suite. In terms of operational characterization, our analyses quantify the removal efficiency through a characteristic removal time and estimate the poisoning effect of gaseous FPs. In addition, we evaluate the activity and decay heat of the removed gas, which is an aspect crucial for the design of the off-gas unit, and the effect of the bubbling system on the power versus the fuel mass flow rate curve, which is a possible control mechanism. Among our safety-related studies, we first evaluate the void coefficient, determining upper bounds on the helium flow rate in order to avoid prompt supercriticality in case of prompt loss of helium injection. The latter accidental scenario is also analyzed considering the thermal-hydraulic dynamics of the system. We also discuss another accident: complete loss of helium removal.

DOCK3-Associated Neurodevelopmental Disorder-Clinical Features and Molecular Basis.

The protein product of DOCK3 is highly expressed in neurons and has a role in cell adhesion and neuronal outgrowth through its interaction with the actin cytoskeleton and key cell signaling molecules. The DOCK3 protein is essential for normal cell growth and migration. Biallelic variants in DOCK3 associated with complete or partial loss of function of the gene were recently reported in six patients with intellectual disability and muscle hypotonia. Only one of the reported patients had congenital malformations outside of the CNS. Further studies are necessary to better determine the prevalence of DOCK3-associated neurodevelopmental disorders and the frequency of non-CNS clinical manifestations in these patients. Since deficiency of the DOCK3 protein product is now an established pathway of this neurodevelopmental condition, supplementing the deficient gene product using a gene therapy approach may be an efficient treatment strategy.

Downward trends in the global burden of congenital complete hearing loss in children younger than five years from 1990 to 2030.

The global epidemiological data on congenital hearing loss in children is sparse. We aimed to analyse the trends in the burden of complete hearing loss caused by congenital birth defects in children younger than five years from 1990 to 2030. Using data from the Global Burden of Disease (GBD) Study 2019, we reported the counts and rates of prevalence and years lived with disability (YLD) by age, sex, and sociodemographic index (SDI). We also forecasted the prevalence rates until 2030 through the autoregressive integrated moving average (ARIMA) and Bayesian age-period-cohort (BAPC) models. We observed a global prevalence rate of 15.4 (95% uncertainty interval (UI) = 5.8 to 33.8) and a YLD rate of 3.3 (95% UI = 1.1 to 7.1) per 100 000 population in 2019, with both showing downward trends from 1990 to 2019. Regionally, Oceania had the highest prevalence (47.2; 95% UI = 18.8 to 96.6) and YLD (10; 95% UI = 3.2 to 22.8) rates, while Central Europe had the lowest rates. Nationally, the prevalence (85.0; 95% UI = 36.8 to 166.8) and YLD (17.9; 95% UI = 6.6 to 36.9) rates were highest in Myanmar and lowest in Peru. Only the United States of America (2.6%; 95% UI = -4.6 to 14.4) and Norway (0.6%; 95% UI = -6.7 to 16.2) showed upward trends. Compared to girls, the prevalence and YLD rates were higher for boys at global, regional, and five SDI quintile levels, except for Eastern Sub-Saharan Africa. At the global level, downward trends were predicted in prevalence rates from 2019 to 2030 between boys and girls. Although the global burden of childhood congenital complete hearing loss showed inequalities across locations, sexes, and age groups, we found decreases in the global prevalence rates between 1990 and 2019 and predicted decreases from 2019 to 2030. Better prevention of infectious aetiologies, improving genetic diagnoses, and hearing restoration could alleviate this burden.

CRISPR-Cas9 Gene Editing in T Cells Induces Site-Specific Chromosome Loss.

CRISPR-Cas9 gene editing in T cells can lead to partial or complete loss of the targeted chromosome.

Transactivation by partial function P53 family mutants is increased by the presence of G-quadruplexes at a promoter site

The effect of mutations in the P53 family of transcription factors on their biological functions, including partial or complete loss of transcriptional activity, has been confirmed several times. At present, P53 family proteins showing partial loss of activity appear to be promising potential candidates for the development of novel therapeutic strategies which could restore their transcriptional activity. In this context, it is important to employ tools to precisely monitor their activity; in relation to this, non-canonical DNA secondary structures in promoters including G-quadruplexes (G4s) were shown to influence the activity of transcription factors. Here, we used a defined yeast assay to evaluate the impact of differently modeled G4 forming sequences on a panel of partial function P53 family mutant proteins. Specifically, a 22-mer G4 prone sequence (derived from the KSHV virus) and five derivatives that progressively mutate characteristic guanine stretches were placed upstream of a minimal promoter, adjacent to a P53 response element in otherwise isogenic yeast luciferase reporter strains. The transactivation ability of cancer-associated P53 (TA-P53α: A161T, R213L, N235S, V272L, R282W, R283C, R337C, R337H, and G360V) or Ectodermal Dyplasia syndromes-related P63 mutant proteins (ΔN-P63α: G134D, G134V and inR155) were tested. Our results show that the presence of G4 forming sequences can increase the transactivation ability of partial function P53 family proteins. These observations are pointing to the importance of DNA structural characteristics for accurate classification of P53 family proteins functionality in the context of the wide variety of TP53 and TP63 germline and somatic mutations.

Parameters influencing the temporal behavior of adhesion on the build plate in fused filament fabrication

ABSTRACT Fused filament fabrication, also known as material extrusion, is an additive manufacturing process used in many industries. Despite its widespread application, common issues like an unwanted deformation of the part to be printed during the process are rarely investigated. These failures, called warping, can be avoided by a sufficient adhesion between build surface and part. Although printing processes can last up to several days, the time dependencies and the mechanism causing adhesion are poorly understood. For this reason, the time dependence of adhesion between polylactic acid and polyamide as printing materials and different building surfaces will be investigated. The adhesion forces can change up to 60% within 20 minutes dependent on the build surface temperature. Higher build surface temperatures lead to a stronger change. These results indicate that besides mechanical adhesion other mechanisms could be involved. Adhesion measurements before and after sandblasting the build surfaces support this. For brass and borosilicate glass as build surface materials, a complete loss of adhesion was observed, whereas it did not change for Pertinax. These overall results lead to the assumption that adhesion occurs because of ionic bond onto brass surfaces and because of hydrogen bond onto borosilicate glass and Pertinax.

Cellular communication and fusion regulate cell fusion, trap morphogenesis, conidiation, and secondary metabolism in Arthrobotrys oligospora

Signal-mediated cell fusion is vital for colony development in filamentous fungi. Arthrobotrys oligospora is a representative nematode-trapping (NT) fungus that produces adhesive networks (traps) to capture nematodes. Here, we characterized Aoadv-1, Aoso, Aoham-6, and Aoham-5 of A. oligospora, homologs of proteins involved in cellular communication and fusion in the model fungus Neurospora crassa. The deletion of four genes resulted in the complete loss of cell fusion, and traps produced by mutants did not close to form mycelial rings but were still capable of capturing nematodes. The absence of these genes inhibits aerial mycelial extension, slows colony growth, and increases mycelial branching. In addition, the mutants showed reduced sporulation capacity and tolerance to oxidative stress, increased sensitivity to SDS, and disturbed lipid droplet accumulation and autophagy. In addition, transcriptome and metabolomic analyses suggested that Aoadv-1 and Aoso are involved in multiple cellular processes and secondary metabolism. Our results revealed that Aoadv-1, Aoso, Aoham-6, and Aoham-5 regulate mycelial growth and trap morphogenesis through cell fusion, which contributed to elucidating the molecular mechanisms of cellular communication regulating mycelial development and trap morphogenesis in NT fungi.

Биологическая борьба с фитофторозом картофеля, вызываемым Phytophthora infestans

Abstract. Potato late blight caused by Phytophthora infestans is a serious disease of potatoes (Solanum tuberosum) and is a common disease in all potato growing regions of Russia. However, successful cultivation of potatoes requires a high level of knowledge and skills from the agronomist. To avoid losses in yield and quality, an average of seven to eight fungicide treatments against this disease are carried out annually. It costs time and money and pollutes the environment. In traditional cultivation, the disease is controlled with the costly application of chemical pesticides. Treatment of tubers with chemicals is effective in reducing tuber-borne infections, but the use of chemicals is dangerous, harmful to beneficial microorganisms, and expensive. In addition, infected tubers should not be stored as they will rot. If the infection is not dealt with, there is a risk of complete loss of the crop. A lot of money has been invested in research and breeding, however, late blight is still the most important disease in potato cultivation. If in some years or regions the disease manifests itself slowly and not very aggressively, in other regions it causes significant crop losses. On the other hand, in agriculture, it is controlled with a comprehensive control strategy, which also includes a wide range of cultural and preventive measures, such as the biological method. Among the various methods in the protection of plants from diseases, the biological method is currently an important share. The mentioned biological method among the means uses special microorganisms, which are characterized by a strong antagonistic reaction in relation to specific pathogens. Scientific novelty lies in the fact that biological preparations showed excellent field performance against late blight in the foothill zone of North Ossetia-Alania. The aim of the study was to test whether the biological defense method against Phytophthora infestans is suitable in the Piedmont zone of the Republic RNO-Alania. Researches were carried out according to the methods accepted in potato breeding according to the recommendations of the All-Russian Institute of Plant Industry, VIR and VIZR. According to the results obtained in field experiments show that in all years of research biopreparations significantly reduced infestation of tubers of phytophthora infestans. Biopreparation “BisolbiSan”, which was used for tubers dressing and spraying of plants four times during the growing season, showed the best protective effect against phytophthora infestans in comparison with other preparations.

Impact of BA.1, BA.2, and BA.4/BA.5 Omicron mutations on therapeutic monoclonal antibodies

The emergence of Omicron SARS-CoV-2 subvariants (BA.1, BA.2, BA.4, and BA.5), with an unprecedented number of mutations in their receptor-binding domain (RBD) of the spike-protein, has fueled a resurgence of COVID-19 infections, posing a major challenge to the efficacy of existing vaccines and monoclonal antibody (mAb) therapeutics. We conducted a systematic molecular dynamics (MD) simulation to investigate how the RBD mutations of these subvariants affect the interactions with broad mAbs including AstraZeneca (COV2-2196 and COV2-2130), Brii Biosciences (BRII-196), Celltrion (CT-P59), Eli Lilly (LY-CoV555 and LY-CoV016), Regeneron (REGN10933 and REGN10987), Vir Biotechnology (S309), and S2X259. Our results show a complete loss of binding for COV2-2196, BRII-196, CT-P59, and LY-CoV555 with all Omicron RBDs. Additionally, REGN10987 totally loses its binding with BA.1, but retains a partial binding with BA.2 and BA.4/5. The binding reduction is significant for LY-CoV016 and REGN10933 but moderate for COV2-2130. S309 and S2X259 retain their binding with BA.1 but exhibit decreased binding with other subvariants. We introduce a mutational escape map for each mAb to identify the key RBD sites and the corresponding critical mutations. Overall, our findings suggest that the majority of therapeutic mAbs have diminished or missing activity against Omicron subvariants, indicating the urgent need for a new therapeutic mAb with a better design.

Loss of αβ but not γδ Tcells in chickens causes a severe phenotype.

The availability of genetically modified mice has facilitated the study of mammalian Tcells. No model has yet been developed to study these cells in chickens, an important livestock species with a high availability of γδ Tcells. To investigate the role of γδ and αβ Tcell populations in birds, we generated chickens lacking these Tcell populations. This was achieved by genomic deletion of the constant region of the Tcell receptor γ or β chain, leading to a complete loss of either γδ or αβ Tcells. Our results show that a deletion of αβ Tcells but not γδ Tcells resulted in a severe phenotype in KO chickens. The αβ Tcell KO chickens exhibited granulomas associated with inflammation of the spleen and the proventriculus. Immunophenotyping of αβ Tcell KO chickens revealed a significant increase in monocytes and expectedly the absence of CD4+ Tcells including FoxP3+ regulatory Tcells. Surprisingly there was no increase of γδ Tcells. In addition, we observed a significant decrease in immunoglobulins, B lymphocytes, and changes in the bursa morphology. Our data reveal the consequences of Tcell knockouts in chickens and provide new insights into their function in vertebrates.