The N-terminal dimerization domains of human and Drosophila CTCF have similar functionality.

BACKGROUND: CTCF is highly likely to be the ancestor of proteins that contain large clusters of C2H2 zinc finger domains, and its conservation is observed across most bilaterian organisms. In mammals, CTCF is the primary architectural protein involved in organizing chromosome topology and mediating enhancer-promoter interactions over long distances. In Drosophila, CTCF (dCTCF) cooperates with other architectural proteins to establish long-range interactions and chromatin boundaries. CTCFs of various organisms contain an unstructured N-terminal dimerization domain (DD) and clusters comprising eleven zinc-finger domains of the C2H2 type. The Drosophila (dCTCF) and human (hCTCF) CTCFs share sequence homology in only five C2H2 domains that specifically bind to a conserved 15 bp motif. RESULTS: Previously, we demonstrated that CTCFs from different organisms carry unstructured N-terminal dimerization domains (DDs) that lack sequence homology. Here we used the CTCFattP(mCh) platform to introduce desired changes in the Drosophila CTCF gene and generated a series of transgenic lines expressing dCTCF with different variants of the N-terminal domain. Our findings revealed that the functionality of dCTCF is significantly affected by the deletion of the N-terminal DD. Additionally, we observed a strong impact on the binding of the dCTCF mutant to chromatin upon deletion of the DD. However, chromatin binding was restored in transgenic flies expressing a chimeric CTCF protein with the DD of hCTCF. Although the chimeric protein exhibited lower expression levels than those of the dCTCF variants, it efficiently bound to chromatin similarly to the wild type (wt) protein. CONCLUSIONS: Our findings suggest that one of the evolutionarily conserved functions of the unstructured N-terminal dimerization domain is to recruit dCTCF to its genomic sites in vivo.

Excessive α-ß Oscillations Mark Enlarged Motor Sign Severity and Parkinson's Disease Duration.

BACKGROUND: ß Oscillations in the subthalamic nucleus (STN) have been proven to contribute to Parkinson's disease (PD), but the exact borders of ß subbands vary substantially across the studies, and information regarding heterogeneity of ß rhythmic activity is still limited. Recently, α oscillations in the basal ganglia have also become the focus of PD research. OBJECTIVES: The aim was to study rhythmic oscillations in the STN in PD patients to identify different subbands with stable oscillatory peaks within a broad α-ß range and to establish their associations with motor symptoms. METHODS: Local field potentials inside the STN were recorded during deep brain stimulation (DBS) surgeries. After calculating power spectra and extracting an aperiodic component, oscillatory peaks in the 8- to 35-Hz range with amplitude exceeding 90th percentile were clustered into three bands. Peak parameters were estimated for two lower subbands. Clinical features were compared in patients with and without oscillation peaks in the lowest α-ß subband. RESULTS: We isolated α-ß (8-15 Hz), ß (15-25 Hz), and ß-γ (25-35 Hz) subbands within the 8- to 35-Hz spectral range using oscillatory parameters and Ward's hierarchical clustering. Additional α-ß oscillatory peaks were found in about half of patients with ß peaks; they were located more ventrally compared to ß. We have found a significant increase in disease duration, bradykinesia, and rigidity scores in the group with additional α-ß peaks. CONCLUSIONS: Increased α-ß oscillations may emerge as additional phenomena complementing ß oscillations; they may mark disease progression in PD and affect DBS stimulation setup. © 2023 International Parkinson and Movement Disorder Society.

Diphtheria, tetanus, and pertussis immunity among healthcare professionals and pregnant women in the Moscow region, Russian federation: A preliminary cross-sectional study.

Despite more than 50 years of primary immunization against diphtheria, pertussis, and tetanus in Russia, complicated illnesses, including fatal ones, still occur. The goal of this preliminary cross-sectional study is to see how well pregnant women and healthcare workers are protected against diphtheria, pertussis, and tetanus. The required sample size (pregnant women and healthcare professionals, as well as pregnant women of two age categories) for this preliminary cross-sectional study was calculated using a confidence value of 0.95 and a probability of 0.05. The required number of participants in each group calculated sample size must be at least 59 people. In the Moscow region (Solnechnogorsk city, Russia), a cross-sectional study of pregnant patients and healthcare professionals interacting with children regularly as part of their job from numerous medical organizations was conducted in the year 2021 (n = 655). Antibodies to diphtheria, tetanus, and pertussis toxoids and microorganisms were measured using an enzyme-linked immunosorbent assay (ELISA). The STATISTICA and IBM SPSS Statistics 26.0 were used to process the study results statistically. Descriptive statistics methods, the Mann-Whitney U-test, discriminant analysis with the stepwise selection and analysis of ROC-curves were applied. IgG against diphtheria was found in 99.5% of pregnant women, tetanus in 91.5%, and pertussis in only 36.5%. According to the results of the discriminant analysis, the value of IgG to pertussis is linked to the value of IgA to pertussis and the gestational periods. Immunity to diphtheria was discovered in 99.1% of medical personnel, tetanus in 96.9%, and pertussis in 43.9%, no significant variations with age. When comparing the levels of immunity of pregnant women and healthcare professionals, it was shown that healthcare workers have greater levels of immunity against diphtheria and tetanus. The novel contribution of this study is that it will reveal the proportion of those vulnerable to pertussis, diphtheria, and tetanus among health workers and pregnant women in all age groups under the current national immunization program in Russia. Considering the data obtained from the preliminary cross-sectional study, we believe that it is necessary to conduct a full-scale study on a larger sample and, based on that, make certain changes to the national immunization program in Russia.

The Role of Different Types of microRNA in the Pathogenesis of Breast and Prostate Cancer.

Micro ribonucleic acids (microRNAs or miRNAs) form a distinct subtype of non-coding RNA and are widely recognized as one of the most significant gene expression regulators in mammalian cells. Mechanistically, the regulation occurs through microRNA binding with its response elements in the 3'-untranslated region of target messenger RNAs (mRNAs), resulting in the post-transcriptional silencing of genes, expressing target mRNAs. Compared to small interfering RNAs, microRNAs have more complex regulatory patterns, making them suitable for fine-tuning gene expressions in different tissues. Dysregulation of microRNAs is well known as one of the causative factors in malignant cell growth. Today, there are numerous data points regarding microRNAs in different cancer transcriptomes, the specificity of microRNA expression changes in various tissues, and the predictive value of specific microRNAs as cancer biomarkers. Breast cancer (BCa) is the most common cancer in women worldwide and seriously impairs patients' physical health. Its incidence has been predicted to rise further. Mounting evidence indicates that microRNAs play key roles in tumorigenesis and development. Prostate cancer (PCa) is one of the most commonly diagnosed cancers in men. Different microRNAs play an important role in PCa. Early diagnosis of BCa and PCa using microRNAs is very useful for improving individual outcomes in the framework of predictive, preventive, and personalized (3P) medicine, thereby reducing the economic burden. This article reviews the roles of different types of microRNA in BCa and PCa progression.

New Preparative Approach to Purer Technetium-99 Samples-Tetramethylammonium Pertechnetate: Deep Understanding and Application of Crystal Structure, Solubility, and Its Conversion to Technetium Zero Valent Matrix.

99Tc is one of the predominant fission products of 235U and an important component of nuclear industry wastes. The long half-life and specific activity of 99Tc (212,000 y, 0.63 GBq g-1) makes Tc a hazardous material. Two principal ways were proposed for its disposal, namely, long-term storage and transmutation. Conversion to metal-like technetium matrices is highly desirable for both cases and for the second one the reasonably high Tc purity was important too. Tetramethylammonium pertechnetate (TMAP) was proposed here as a prospective precursor for matrix manufacture. It provided with very high decontamination factors from actinides (that is imperative for transmutation) by means of recrystallisation and it was based on the precise data on TMAP solubility and thermodynamics accomplished in the temperature range of 3-68 °C. The structure of solid pertechnetates were re-estimated with precise X-ray structure solution and compared to its Re and Cl analogues and tetrabutylammonium analogue as well. Differential thermal and evolved gas analysis in a flow of Ar-5% H2 gas mixture showed that the major products of thermolysis were pure metallic technetium in solid matrix, trimethylammonium, carbon dioxide, and water in gas phase. High decontamination factors have been achieved when TMAP was used as an intermediate precursor for Tc.

Molecular Mechanisms of Scombroid Food Poisoning.

Scombroid food poisoning (SFP) is a foodborne disease that develops after consumption of fresh fish and, rarely, seafood that has fine organoleptic characteristics but contains a large amount of exogenous histamine. SFP, like other food pseudo-allergic reactions (FPA), is a disorder that is clinically identical to allergic reactions type I, but there are many differences in their pathogenesis. To date, SFP has been widespread throughout the world and is an urgent problem, although exact epidemiological data on incidence varies greatly. The need to distinguish SFP from true IgE-associated allergy to fish and seafood is one of the most difficult examples of the differential diagnosis of allergic conditions. The most important difference is the absence of an IgE response in SFP. The pathogenesis of SFP includes a complex system of interactions between the body and chemical triggers such as exogenous histamine, other biogenic amines, cis-urocanic acid, salicylates, and other histamine liberators. Because of the wide range of molecular pathways involved in this process, it is critical to understand their differences. This may help predict and prevent poor outcomes in patients and contribute to the development of adequate hygienic rules and regulations for seafood product safety. Despite the vast and lengthy history of research on SFP mechanisms, there are still many blank spots in our understanding of this condition. The goals of this review are to differentiate various molecular mechanisms of SFP and describe methods of hygienic regulation of some biogenic amines that influence the concentration of histamine in the human body and play an important role in the mechanism of SFP.

The Essential Role of Prolines and Their Conformation in Allosteric Regulation of Kaiso Zinc Finger DNA-Binding Activity by the Adjacent C-Terminal Loop.

Kaiso is a methyl-DNA-binding protein containing three C2H2 zinc fingers with a C-terminal extension that participates in DNA binding. The linker between the last zinc finger and the DNA-binding portion of the extension contains two prolines that are highly conserved in vertebrates and in cognate ZBTB4 and ZBTB38 proteins. Prolines provide chain rigidity and can exist in cis and trans conformations that can be switched by proline isomerases, affecting protein function. We found that substitution of the conserved proline P588, but not of P577, to alanine, negatively affected KaisoDNA-binding according to molecular dynamics simulation and in vitro DNA-binding assays. Molecular dynamics simulations of the Kaiso DNA-binding domain with P588 either substituted to alanine or switched to the cis-conformation revealed similar alterations in the H-bonding network and uncovered allosteric effects leading to structural rearrangements in the entire domain that resulted in the weakening of DNA-binding affinity. The substitution of proline with a large hydrophobic residue led to the same negative effects despite its ability to partially rescue the intrinsic DNA-binding activity of the C-terminal loop. Thus, the presence of the C-terminal extension and cis-conformation of proline residues are essential for efficient Kaiso-DNA binding, which likely involves intramolecular tension squeezing the DNA chain.

Analysis of the Face Mask Use by Public Transport Passengers and Workers during the COVID-19 Pandemic.

(1) Background: The use of face masks and gloves in public places directly shows the commitment of the population to the established regulations. Public transport is one of the most-at-risk places of contamination. The aim of the study was to analyze the face mask use by public transport passengers and workers during the COVID-19 pandemic. (2) Methods: Public transport passengers and workers were surveyed. Periodic intermittent selective observation was used to gauge the level of adherence to the established regulations among public transport passengers. Factor analysis was used to identify factors determining the face-mask-wearing comfort. (3) Results: The majority of passengers (87.5%) and all transport workers (100%) used face masks and gloves. Most of the users wore only face masks. Only 41.6% of passengers and 74.7% of transport workers wore face masks correctly. Motivational attitudes at the implementation of preventive measures were determined: established regulations in the public place (55.8%) and the protection of one's own health and the health of family members (44.2%). Only 22.5% of those wearing face masks believed that doing so will have any effect on the spread of an infectious disease, and 10.8% wore masks to maintain the health of people around themselves. A low level of social responsibility was demonstrated. For 53.4% of workers, face mask wearing was uncomfortable. The majority of workers had adverse reactions to mask wearing: feeling short of breath (52.8%), hyperemia of face skin (33.8%), and facial hyperhidrosis (67.4%). (4) Conclusions: The comfort of wearing a mask is determined by adverse reactions occurrence, the properties of the mask, working conditions, and the duration of wearing the face mask. It is necessary to develop recommendations to reduce wearing discomfort. These recommendations, along with methods of raising the social responsibility of the population, can contribute to a greater commitment of the population to non-specific prevention measures.

Study of the Deep Processes of COVID-19 in Russia: Finding Ways to Identify Preventive Measures.

The novel coronavirus disease 2019 (COVID-19) pandemic has had a huge impact on all areas of human life. Since the risk of biological threats will persist in the future, it is very important to ensure mobilization readiness for a prompt response to the possible emergence of epidemics of infectious diseases. Therefore, from both a theoretical and practical standpoint, it is currently necessary to conduct a thorough examination of the COVID-19 epidemic. The goal of this research is to investigate the underlying processes that led to the COVID-19 pandemic in Russia and to identify ways to improve preventive measures and ensure mobilization readiness for a quick response to potential COVID-19-like pandemics. This research will analyze the daily dynamics of the number of infection cases and the number of new lethal cases of COVID-19. We analyzed the daily number of new cases of COVID-19 infection N(d), the daily number of new lethal cases L(d), their percentage ratio L(d)/N(d) 100% in Russia for 2 years of the pandemic (from the beginning of the pandemic to 23 March 2022), the rate of increase and decrease of these indicators (dN(d)/dd and dL(d)/dd), as well as their spectra created on the basis of wavelet analysis. Wavelet analysis of the deep structure of the N(d) and L(d) wavelet spectra made it possible to identify the presence of internal cycles, the study of which makes it possible to predict the presence of days with the maximum number of infections and new deaths in a pandemic similar to COVID-19 and outline ways and methods for improving preventive measures and measures to ensure mobilization readiness for a rapid response to the potential emergence of pandemics similar to COVID-19.

Attenuation of neural responses in subthalamic nucleus during internally guided voluntary movements in Parkinson's disease.

The proposed models of segregated functional loops describe the organization of motor control over externally triggered (ET) and internally guided (IG) movements. The dopamine deficiency in Parkinson's disease (PD) is considered to cause a disturbance in the functional loop regulating IG movements. At the same time, the neural mechanisms of movement performance and the role of basal ganglia in motor control remain unclear.The aim of this study was to compare neuronal responses in the subthalamic nucleus (STN) during ET and IG movements in PD. We found and analyzed 26 sensitive neurons in 12 PD patients who underwent surgery for implantation of electrodes for deep brain stimulation. We also analyzed the local field potentials (LFP) of the STN of six patients during the postoperative period. Patients were asked to perform voluntary movements (clenching and unclenching the fist) evoked by verbal command (ET) or self-initiated (IG). We showed heterogeneity of neuronal responses and did not find sensitive neurons associated with only one type of movement. Most cells were characterized by leading responses, indicating that the STN has an important role in movement initiation. At the same time, we found attenuation of motor responses during IG movement vs. stable responses during ET movements. LFP analysis also showed attenuation of beta desynchronization during multiple IG movements.We propose that stable neuronal response to ET movements is associated with the reboot of the motor program for each movement, while attenuation of responses to IG movement is associated with single motor program launching for multiple movements.

Medical Care for Tuberculosis-HIV-Coinfected Patients in Russia with Respect to a Changeable Patients' Structure.

To date, tuberculosis (TB) remains the primary cause of mortality in human immunodeficiency virus (HIV) patients in Russia. Since the beginning of 2000, a sharp change in the HIV patients' structure, to the main known risk factors for HIV infection has taken place in Russia. The transmission of HIV through injectable drug use has begun to decline significantly, giving way to the prevalence of sexual HIV transmission today. These changes may require adjustments to organizational approaches to anti-TB care and the treatment of HIV-positive patients. Our study is aimed at identifying changes in TB-HIV coinfection patients' structures in 2019 compared to 2000. Based on the results obtained, our goal was to point out the parameters that need to be taken into account when developing approaches to improve the organization of TB control care for people with HIV infection. We have carried out a cross-sectional, retrospective, epidemiological study using government TB registry data from four regions in two federal districts of Russia in 2019. The case histories of 2265 patients from two regions with high HIV prevalence, which are part of the Siberian Federal District of Russia, and 89 patient histories from two regions of low HIV prevalence, which are part of the Central Federal District of Russia, were analyzed. We found that parenteral transmission (69.4%) remains the primary route of HIV transmission among the TB-HIV coinfected. The unemployed of working age without disability account for 80.2% of all coinfected people, while the formerly incarcerated account for 53.7% and the homeless account for 4.1%. Those with primary multidrug-resistant TB (MDR-TB) comprise 56.2% of HIV-TB patients. When comparing the incidence of coinfection with HIV among TB patients, statistically significant differences were obtained. Thus, the chances of coinfection increased by 4.33 times among people with active TB (95% CI: 2.31; 8.12), by 2.97 times among people with MDR-TB (95% CI: 1.66; 5.32), by 5.2 times in people with advanced processes in the lungs, including destruction, (95% CI: 2.78; 9.7), as well as by 10.3 times in the case of death within the first year after the TB diagnosis (95% CI: 2.99; 35.5). The absence of data for the presence of TB during preventive examination was accompanied by a decrease in the chances of detecting coinfection (OR 0.36; 95% CI: 0.2; 0.64). We have identified the probable causes of the high incidence of TB among HIV-infected: HIV-patient social maladaptation usually results in delayed medical care, leading to TB treatment regimen violations. Furthermore, self-administration of drugs triggers MDR-TB within this group. Healthcare providers should clearly explain to patients the critical importance of immediately seeking medical care when initial TB symptoms appear.

Oscillations of pause-burst neurons in the STN correlate with the severity of motor signs in Parkinson's disease.

BACKGROUND: Oscillatory activity in the subthalamic nucleus (STN) in Parkinson's disease (PD) is under extensive study. While rhythmic features of local field potentials are implicated in the manifestation of PD motor signs, less is known about single unit activity (SUA). SUA parameters inside the STN show significant heterogeneity, and various firing patterns may contribute unequally to PD pathophysiology. OBJECTIVES: We searched for correlations between SUA parameters and PD motor signs, taking neuronal activity patterns into account. METHODS: 829 spike trains for STN SUA were recorded during 25 DBS surgeries. We have isolated three firing patterns (tonic, irregular-burst and pause-burst) and, using mixed linear models, examined several spiking parameters and burst descriptors (for the last two patterns) for their correlation with UPDRS-III PD motor signs in the contralateral hemibody. RESULTS: The predominance of pause-burst as opposed to tonic activity was associated with a higher PD motor sign severity UPDRS-III. Spike synchronization in the alpha and beta range correlated positively with bradykinesia scores only for pause-burst neurons, while spike synchrony in the theta frequency (4-8 Hz) in these neurons showed an inverse correlation with bradykinesia scores. Other patterns showed no correlation with PD motor signs. CONCLUSIONS: Our work demonstrates the PD motor state is associated with distinct changes in firing patterns and oscillatory synchronization that can be associated with PD motor sign severity. Here, pause-burst patterns were identified as most informative, potentially reflecting a progressive shift from tonic to burst to rhythmic activity in the alpha and beta frequency bands in the parkinsonian state.

Assessment of Hygiene Indicators When Using Gloves by Transport Workers in Russia during the COVID-19 Pandemic.

The COVID-19 outbreak represents a global public health emergency. National governments have gradually introduced restrictive measures. Using respiratory protective equipment (face masks) and gloves was essential practice without specific infection control measures or guidelines. This study aimed to assess hygiene indicators when using gloves by transport workers in Russia during the COVID-19 pandemic and to develop integral indicators and recommendations for wearing gloves for workers for whom this is a mandatory requirement. For this purpose, 1103 transport workers were surveyed using a questionnaire. We investigated the hygiene aspects of gloves and evaluated the bacterial contamination of the contact side of the gloves based on the wash results. We assessed the socio-demographic characteristics of the respondents, the duration of the work shift, the frequency of use of types of gloves, skin manifestations, the degree of comfort, and bacterial growth. We carried out the ranking according to comfort, the absence of adverse dermatological reactions when wearing gloves, and bacterial contamination of the inner surface of the gloves. It has been identified that it is necessary to use a comprehensive assessment of gloves to create a register of protective equipment, taking into account the frequency with which it was worn, the severity of the skin condition, comfort, and bacterial contamination.

Sanitary Aspects of Countering the Spread of COVID-19 in Russia.

Due to the conditions that cause the spread of COVID-19, national health systems worldwide are under severe strain. Most countries face similar difficulties such as a lack of medical personnel and equipment and tools for diagnosis and treatment, overrun hospitals, and forced restriction of planned medical care. Public authorities in healthcare take the following measures due to increased pressure: limiting the transmission and spread of the virus (social distancing and quarantine), mobilizing medical personnel, ensuring the availability of diagnostic and treatment tools, and providing a sufficient number of premises, which are not always suitable for the provision of medical care (buildings and structures). To date, the stages of management decision-making to counter coronavirus infection and the risk of COVID-19 transmission at various facilities have not been analyzed. The authors propose a methodology for assessing the COVID-19 transmission risk at various social and transport facilities. A survey of 1325 respondents from Moscow demonstrated the most significant risk factors, such as visitation avoidance, infection risk, and facemask wearing. Risk categories were determined and objects classified according to high, medium, and low-risk levels.

Indoor Environmental Quality in Dwellings and Lifestyle Behaviors during the COVID-19 Pandemic: Russian Perspective.

The novel coronavirus (COVID-19) outbreak is a public health emergency of international concern, and as a response, public health authorities started enforcing preventive measures like self-isolation and social distancing. The enforcement of isolation has consequences that may affect the lifestyle-related behavior of the general population. Quarantine encompasses a range of strategies that can be used to detain, isolate, or conditionally release individuals or populations infected or exposed to contagious diseases and should be tailored to circumstances. Interestingly, medical students may represent an example of how the COVID-19 pandemic can form new habits and change lifestyle behaviors. We conducted a web-based survey to assess changes in lifestyle-related behavior of self-isolated medical students during the COVID-19 pandemic. Then we analyzed the sanitary-hygienic regulations of the Russian Federation to determine the requirements for healthy buildings. Results showed that during the pandemic, the enforcement of isolation affects medical students' lifestyle-related behavior and accompanies an increase in non-communicable diseases (NCDs). Indoor environmental quality (IEQ) and healthy buildings are cutting-edge factors in preventing COVID-19 and NCDs. The Russian sanitary-hygienic regulations support improving this factor with suitable requirements for ventilation, sewage, waste management, and disinfection. Herein, assessing isolation is possible through the hygienic self-isolation index.

COVID-19 in Dental Settings: Novel Risk Assessment Approach.

The novel coronavirus (COVID-19) outbreak is a public health emergency of international concern, and this emergency led to postponing elective dental care procedures. The postponing aimed to protect the public from an unknown risk caused by COVID-19. At the beginning of the outbreak, for public health authorities, the aerosol-generating procedures and the close proximity between dental care workers and patients in dentistry represented sufficient justification for the delay of dental visits. Dental care is a priority, and for many years, studies have proven that the lack and delay of dental care can cause severe consequences for the oral health of the general population, which can cause a high global burden of oral diseases. Safety is necessary while resuming dental activities, and risk assessment is an efficient method for understanding and preventing the COVID-19 infectious threats facing the dental industry and affecting dental care workers and patients. In this study, for safe dental care delivery, we adapted risk assessment criteria and an approach and an occupational classification system. Based on those tools, we also recommend measures that can help to minimize infectious risk in dental settings.

Is there a single beta oscillation band interfering with movement in Parkinson's disease?

Beta oscillations in basal ganglia are considered to contribute to motor dysfunction in Parkinson's disease (PD). However, there is a high variety in frequency borders for beta oscillations between studies, which complicates the comparison and interpretation of results. Here we aimed to study the homogeneity of oscillations in the broad "beta" range (8-30 Hz) and their implication to motor functioning in PD. For this purpose, we recorded local field potentials (LFP) in the subthalamic nucleus (STN) during 34 deep brain stimulation surgeries. We identified spectral features of LFP recordings in the range 8-30 Hz to search for candidate sub-regions of stable oscillations and assessed their association with clinical scores on the contralateral side of the body and sensitivity to motor tests. Lower frequency oscillations (8-16 Hz) had a significant positive association with bradykinesia score. During voluntary movements, we observed a significant increase in LFP power in the 12-16 Hz range and a decrease in the 18-26 Hz range. We may conclude that the 8-30 Hz oscillation range includes oscillations with different functional features-sensitivity and responsiveness to movement, and clinical symptoms, which should be taken into account in further studies of beta oscillations association with PD pathophysiology. These data assume the coexistence of several frequency domains within beta range that are modulated in different ways under dopaminergic regulation and motor processing in human STN.

Mechanism and functional role of the interaction between CP190 and the architectural protein Pita in Drosophila melanogaster.

BACKGROUND: Pita is required for Drosophila development and binds specifically to a long motif in active promoters and insulators. Pita belongs to the Drosophila family of zinc-finger architectural proteins, which also includes Su(Hw) and the conserved among higher eukaryotes CTCF. The architectural proteins maintain the active state of regulatory elements and the long-distance interactions between them. In particular, Pita is involved in the formation of several boundaries between regulatory domains that controlled the expression of three hox genes in the Bithorax complex (BX-C). The CP190 protein is recruited to chromatin through interaction with the architectural proteins. RESULTS: Using in vitro pull-down analysis, we precisely mapped two unstructured regions of Pita that interact with the BTB domain of CP190. Then we constructed transgenic lines expressing the Pita protein of the wild-type and mutant variants lacking CP190-interacting regions. We have demonstrated that CP190-interacting region of the Pita can maintain nucleosome-free open chromatin and is critical for Pita-mediated enhancer blocking activity in BX-C. At the same time, interaction with CP190 is not required for the in vivo function of the mutant Pita protein, which binds to the same regions of the genome as the wild-type protein. Unexpectedly, we found that CP190 was still associated with the most of genome regions bound by the mutant Pita protein, which suggested that other architectural proteins were continuing to recruit CP190 to these regions. CONCLUSIONS: The results directly demonstrate role of CP190 in insulation and support a model in which the regulatory elements are composed of combinations of binding sites that interact with several architectural proteins with similar functions.

A Non-stop identity complex (NIC) supervises enterocyte identity and protects from premature aging.

A hallmark of aging is loss of differentiated cell identity. Aged Drosophila midgut differentiated enterocytes (ECs) lose their identity, impairing tissue homeostasis. To discover identity regulators, we performed an RNAi screen targeting ubiquitin-related genes in ECs. Seventeen genes were identified, including the deubiquitinase Non-stop (CG4166). Lineage tracing established that acute loss of Non-stop in young ECs phenocopies aged ECs at cellular and tissue levels. Proteomic analysis unveiled that Non-stop maintains identity as part of a Non-stop identity complex (NIC) containing E(y)2, Sgf11, Cp190, (Mod) mdg4, and Nup98. Non-stop ensured chromatin accessibility, maintaining the EC-gene signature, and protected NIC subunit stability. Upon aging, the levels of Non-stop and NIC subunits declined, distorting the unique organization of the EC nucleus. Maintaining youthful levels of Non-stop in wildtype aged ECs safeguards NIC subunits, nuclear organization, and suppressed aging phenotypes. Thus, Non-stop and NIC, supervise EC identity and protects from premature aging.

Voluntary movements cause beta oscillations increase and broadband slope decrease in the subthalamic nucleus of parkinsonian patients.

Periodic features of local field potentials (LFP) are extensively studied to establish the pathophysiological features contributing to Parkinson's disease (PD). Pathological LFP synchronization in the subthalamic nucleus (STN) was assumed to link with motor signs of PD. Commonly, the association between oscillations and clinical signs is studied while the patients are at rest. However, changes in LFPs during movement may reflect particular traits of motor processing in the basal ganglia under PD. Recently, the aperiodic 1/f broadband component of LFP spectra has attracted the attention of researchers because it may provide meaningful information about the neural activity in the brain. Here, we compared LFP signals in the STN of parkinsonian patients at rest and during hand movements occasionally followed by leg movements using two approaches, one of which accounts for the aperiodic features of LFP spectra. Using both methods, a significant increase was observed in synchronization in the low beta range during sequent leg but not hand movements. For either movement, there was a significant increase in gamma range synchronization using uncorrected power spectra and a significant decrease in the slope of the aperiodic component for the 1/f-corrected method. These findings may support the claim that the 1/f slope possibly reflects the excitatory/inhibitory projections ratio in the recording site. Only the difference in the slope correlated significantly with motor signs of PD. These data show that the slope of aperiodic component may be a useful measure that is sensitive to the specific state and its changes in the brain.