Natural variation in the zinc-finger-encoding exon of Prdm9 affects hybrid sterility phenotypes in mice.

PRDM9-mediated reproductive isolation was first described in the progeny of Mus musculus musculus (MUS) PWD/Ph and Mus musculus domesticus (DOM) C57BL/6J inbred strains. These male F1 hybrids fail to complete chromosome synapsis and arrest meiosis at prophase I, due to incompatibilities between the Prdm9 gene and hybrid sterility locus Hstx2. We identified 14 alleles of Prdm9 in exon 12, encoding the DNA-binding domain of the PRDM9 protein in outcrossed wild mouse populations from Europe, Asia, and the Middle East, 8 of which are novel. The same allele was found in all mice bearing introgressed t-haplotypes encompassing Prdm9. We asked whether 7 novel Prdm9 alleles in MUS populations and the t-haplotype allele in 1 MUS and 3 DOM populations induce Prdm9-mediated reproductive isolation. The results show that only combinations of the dom2 allele of DOM origin and the MUS msc1 allele ensure complete infertility of intersubspecific hybrids in outcrossed wild populations and inbred mouse strains examined so far. The results further indicate that MUS mice may share the erasure of PRDM9msc1 binding motifs in populations with different Prdm9 alleles, which implies that erased PRDM9 binding motifs may be uncoupled from their corresponding Prdm9 alleles at the population level. Our data corroborate the model of Prdm9-mediated hybrid sterility beyond inbred strains of mice and suggest that sterility alleles of Prdm9 may be rare.

Patent analysis of digital sensors for continuous glucose monitoring.

The high need for optimal diabetes management among an ever-increasing number of patients dictates the development and implementation of new digital sensors for continuous glucose monitoring. The purpose of this work is to systematize the global patenting trends of digital sensors for continuous glucose monitoring and analyze their effectiveness in controlling the treatment of diabetes patients of different ages and risk groups. The Lens database was used to build the patent landscape of sensors for continuous glucose monitoring. Retrospective analysis showed that the patenting of sensors for continuous glucose monitoring had positive trend over the analyzed period (2000-2022). Leading development companies are Dexcom Inc., Abbott Diabetes Care Inc., Medtronic Minimed Inc., Roche Diabetes Care Inc., Roche Diagnostics Operations Inc., Roche Diabetes Care Gmbh, and Ascensia Diabetes Care Holdings Ag, among others. Since 2006, a new approach has emerged where digital sensors are used for continuous glucose monitoring, and smartphones act as receivers for the data. Additionally, telemedicine communication is employed to facilitate this process. This opens up new opportunities for assessing the glycemic profile (glycemic curve information, quantitative assessment of the duration and amplitude of glucose fluctuations, and so on), which may contribute to improved diabetes management. A number of digital sensors for minimally invasive glucose monitoring are patented, have received FDA approval, and have been on the market for over 10 years. Their effectiveness in the clinic has been proven, and advantages and disadvantages have been clarified. Digital sensors offer a non-invasive option for monitoring blood glucose levels, providing an alternative to traditional invasive methods. This is particularly useful for patients with diabetes who require frequent monitoring, including before and after meals, during and after exercise, and in other scenarios where glucose levels can fluctuate. However, non-invasive glucose measurements can also benefit patients without diabetes, such as those following a dietary treatment plan, pregnant women, and individuals during fasting periods like Ramadan. The availability of non-invasive monitoring is especially valuable for patients in high-risk groups and across different age ranges. New world trends have been identified in the patenting of digital sensors for non-invasive glucose monitoring in interstitial skin fluid, saliva, sweat, tear fluid, and exhaled air. A number of non-invasive devices have received the CE mark approval, which confirms that the items meet European health, safety, and environmental protection standards (TensorTip Combo-Glucometer, Cnoga Medical Ltd.; SugarBEAT, Nemaura Medical; GlucoTrack, GlucoTrack Inc.), but are not FDA-approved yet. The above-mentioned sensors have characteristics that make them popular in the treatment of diabetes: they do not require implantation, do not cause an organism reaction to a foreign body, and are convenient to use. In the EU, in order to increase clinical safety and the level of transparency about medical devices, manufacturers must obtain certificates in accordance with Regulation (EU) 2017/745, taking into account the transition period. The development of systems, which include digital sensors for continuous glucose monitoring, mobile applications, and web platforms for professional analysis of glycemic control and implementation of unified glycemic assessment principles in mobile healthcare, represent promising approaches for controlling glycaemia in patients.

Patent landscape review of non-invasive medical sensors for continuous monitoring of blood pressure and their validation in critical care practice.

Objectives: Continuous non-invasive monitoring of blood pressure is one of the main factors in ensuring the safety of the patient's condition in anesthesiology, intensive care, surgery, and other areas of medicine. The purpose of this work was to analyze the current patent situation and identify directions and trends in the application of non-invasive medical sensors for continuous blood pressure monitoring, with a focus on clinical experience in critical care and validation thereof. Materials and methods: The research results reflect data collected up to September 30, 2022. Patent databases, Google Scholar, the Lens database, Pubmed, Scopus databases were used to search for patent and clinical information. Results: An analysis of the patent landscape indicates a significant increase in interest in the development of non-invasive devices for continuous blood pressure monitoring and their implementation in medical practice, especially in the last 10 years. The key players in the intellectual property market are the following companies: Cnsystems Medizintechnik; Sotera Wireless INC; Tensys Medical INC; Healthstats Int Pte LTD; Edwards Lifesciences Corp, among others. Systematization of data from validation and clinical studies in critical care practice on patients with various pathological conditions and ages, including children and newborns, revealed that a number of non-invasive medical sensor technologies are quite accurate and comparable to the "gold standard" continuous invasive blood pressure monitoring. They are approved by the FDA for medical applications and certified according to ISO 81060-2, ISO 81060-3, and ISO/TS 81060-5. Unregistered and uncertified medical sensors require further clinical trials. Conclusion: Non-invasive medical sensors for continuous blood pressure monitoring do not replace, but complement, existing methods of regular blood pressure measurement, and it is expected to see more of these technologies broadly implemented in the practice in the near future.

Public interest in different types of masks and its relationship with pandemic and policy measures during the COVID-19 pandemic: a study using Google Trends data.

Google Trends data have been used to investigate various themes on online information seeking. It was unclear if the population from different parts of the world shared the same amount of attention to different mask types during the COVID-19 pandemic. This study aimed to reveal which types of masks were frequently searched by the public in different countries, and evaluated if public attention to masks could be related to mandatory policy, stringency of the policy, and transmission rate of COVID-19. By referring to an open dataset hosted at the online database Our World in Data, the 10 countries with the highest total number of COVID-19 cases as of 9th of February 2022 were identified. For each of these countries, the weekly new cases per million population, reproduction rate (of COVID-19), stringency index, and face covering policy score were computed from the raw daily data. Google Trends were queried to extract the relative search volume (RSV) for different types of masks from each of these countries. Results found that Google searches for N95 masks were predominant in India, whereas surgical masks were predominant in Russia, FFP2 masks were predominant in Spain, and cloth masks were predominant in both France and United Kingdom. The United States, Brazil, Germany, and Turkey had two predominant types of mask. The online searching behavior for masks markedly varied across countries. For most of the surveyed countries, the online searching for masks peaked during the first wave of COVID-19 pandemic before the government implemented mandatory mask wearing. The search for masks positively correlated with the government response stringency index but not with the COVID-19 reproduction rate or the new cases per million.

Are dental x-rays safe? Content analysis of English and Chinese YouTube videos.

Objective: This study provided a content analysis of English and Chinese YouTube videos related to dental radiation safety. Method: The search string, entered in English and Chinese respectively, was: (dental x-ray safe). The searches were performed and exported with Apify YouTube scraper. By screening the resultant videos and their related videos (as recommended by YouTube), a total of 89 videos were screened. Finally, 45 videos (36 English and nine Chinese) were included and analyzed. The specific information regarding dental radiation was evaluated. The Patient Education Material Assessment Tool for Audiovisual Materials was used to assess understandability and actionability. Results: There was no significant difference between the English and Chinese videos in terms of view count, like count, comment count, and video duration. Half of the videos explicitly reassured the audience that dental x-rays are safe. Two of the English videos specifically stated that dental x-rays do not cause cancers. Numerous analogies were made in regard to radiation dose, such as equivalence to taking a flight or eating some bananas. About 41.7% of the English videos and 33.3% of the Chinese videos mentioned that patients could be further protected from scatter radiation by wearing a lead apron and thyroid collar. Videos had a good understandability score (91.3) but a poor actionability score (0). Conclusions: Some of the analogies and the claimed radiation dose were questionable. One Chinese video even wrongly stated that dental x-rays are nonionizing radiation. The videos generally did not mention their information sources or the underlying radiation protection principles.

"Loved ones are not 'visitors' in a patient's life"-The importance of including loved ones in the patient's hospital stay: An international Twitter study of #HospitalsTalkToLovedOnes in times of COVID-19.

Background: Hospitals are institutions whose primary task is to treat patients. Family-centered care, which considers loved ones as equal partners in patient care, has been gaining recognition in the adult care setting. Our aim was to record experiences of and opinions on communication between hospital-based healthcare providers and patients' loved ones, related but not limited to the rigorous mitigation measures implemented during the COVID-19 pandemic. Methods: The Twitter profile @HospitalsTalkTo and hashtag #HospitalsTalkToLovedOnes were created to interact with the Twitter public between 7 June 2021 and 7 February 2022. Conversations surrounding #HospitalsTalkToLovedOnes were extracted and subjected to natural language processing analysis using term frequency and Markov chain analysis. Qualitative thematic analysis was performed on the 10% most interacted tweets and of tweets mentioning "COVID" from a personal experience-based subset. Results: We collected 4412 unique tweets made or interacted by 7040 Twitter users from 142 different countries. The most frequent words were patient, hospital, care, family, loved and communication. Thematic analysis revealed the importance of communication between patients, patients' loved ones and hospitals; showed that patients and their loved ones need support during a patient's hospital journey; and that pediatric care should be the gold standard for adult care. Visitation restrictions due to COVID-19 are just one barrier to communication, others are a lack of phone signal, no space or time for asking questions, and a complex medical system. We formulate 3 recommendations to improve the inclusion of loved ones into the patient's hospital stay. Conclusions: "Loved ones are not 'visitors' in a patient's life". Irrespective of COVID-19, patient's loved ones need to be included during the patient's hospital journey. Transparent communication and patient empowerment increase patient safety and improve the hospital experience for both the patients and their loved ones. Our findings underline the need for the concept of family-centered care to finally be implemented in adult nursing clinical practice.

COVID-19 Rapid Antigen Tests: Bibliometric Analysis of the Scientific Literature.

As the COVID-19 pandemic continues to disrupt health systems worldwide, conducting Rapid Antigen Testing (RAT) at specified intervals has become an essential part of many people's lives around the world. We identified and analyzed the academic literature on COVID-19 RAT. The Web of Science electronic database was queried on 6 July 2022 to find relevant publications. Publication and citation data were retrieved directly from the database. VOSviewer, a bibliometric software, was then used to relate these data to the semantic content from the titles, abstracts, and keywords. The analysis was based on data from 1000 publications. The most productive authors were from Japan and the United States, led by Dr. Koji Nakamura from Japan (n = 10, 1.0%). The most academically productive countries were in the North America, Europe and Asia, led by the United States of America (n = 266, 26.6%). Sensitivity (n = 32, 3.2%) and specificity (n = 23, 2.3%) were among the most frequently recurring author keywords. Regarding sampling methods, "saliva" (n = 54, 5.4%) was mentioned more frequently than "nasal swab" (n = 32, 3.2%) and "nasopharyngeal swab" (n = 22, 2.2%). Recurring scenarios that required RAT were identified: emergency department, healthcare worker, mass screening, airport, traveler, and workplace. Our bibliometric analysis revealed that COVID-19 RAT has been utilized in a range of studies. RAT results were cross-checked with RT-PCR tests for sensitivity and specificity. These results are consistent with comparable exchanges of methods, results or discussions among laboratorians, authors, institutions and publishers in the involved countries of the world.

Twitter-based crowdsourcing: What kind of measures can help to end the COVID-19 pandemic faster?

Background: Crowdsourcing is a low-cost, adaptable, and innovative method to collect ideas from numerous contributors with diverse backgrounds. Crowdsourcing from social media like Twitter can be used for generating ideas in a noticeably brief time based on contributions from globally distributed users. The world has been challenged by the COVID-19 pandemic in the last several years. Measures to combat the pandemic continue to evolve worldwide, and ideas and opinions on optimal counteraction strategies are of high interest. Objective: This study aimed to validate the use of Twitter as a crowdsourcing platform in order to gain an understanding of public opinion on what measures can help to end the COVID-19 pandemic faster. Methods: This cross-sectional study was conducted during the period from December 22, 2021, to February 4, 2022. Tweets were posted by accounts operated by the authors, asking "How to faster end the COVID-19 pandemic?" and encouraging the viewers to comment on measures that they perceive would be effective to achieve this goal. The ideas from the users' comments were collected and categorized into two major themes - personal and institutional measures. In the final stage of the campaign, a Twitter poll was conducted to get additional comments and to estimate which of the two groups of measures were perceived to be important amongst Twitter users. Results: The crowdsourcing campaign generated seventeen suggested measures categorized into two major themes (personal and institutional) that received a total of 1,727 endorsements (supporting comments, retweets, and likes). The poll received a total of 325 votes with 58% of votes underscoring the importance of both personal and institutional measures, 20% favoring personal measures, 11% favoring institutional measures, and 11% of the votes given just out of curiosity to see the vote results. Conclusions: Twitter was utilized successfully for crowdsourcing ideas on strategies how to end the COVID-19 pandemic faster. The results indicate that the Twitter community highly values the significance of both personal responsibility and institutional measures to counteract the pandemic. This study validates the use of Twitter as a primary tool that could be used for crowdsourcing ideas with healthcare significance.

Promoting Research, Awareness, and Discussion on AI in Medicine Using #MedTwitterAI: A Longitudinal Twitter Hashtag Analysis.

Background: Artificial intelligence (AI) has the potential to reshape medical practice and the delivery of healthcare. Online discussions surrounding AI's utility in these domains are increasingly emerging, likely due to considerable interest from healthcare practitioners, medical technology developers, and other relevant stakeholders. However, many practitioners and medical students report limited understanding and familiarity with AI. Objective: To promote research, events, and resources at the intersection of AI and medicine for the online medical community, we created a Twitter-based campaign using the hashtag #MedTwitterAI. Methods: In the present study, we analyze the use of #MedTwitterAI by tracking tweets containing this hashtag posted from 26th March, 2019 to 26th March, 2021, using the Symplur Signals hashtag analytics tool. The full text of all #MedTwitterAI tweets was also extracted and subjected to a natural language processing analysis. Results: Over this time period, we identified 7,441 tweets containing #MedTwitterAI, posted by 1,519 unique Twitter users which generated 59,455,569 impressions. The most common identifiable locations for users including this hashtag in tweets were the United States (378/1,519), the United Kingdom (80/1,519), Canada (65/1,519), India (46/1,519), Spain (29/1,519), France (24/1,519), Italy (16/1,519), Australia (16/1,519), Germany (16/1,519), and Brazil (15/1,519). Tweets were frequently enhanced with links (80.2%), mentions of other accounts (93.9%), and photos (56.6%). The five most abundant single words were AI (artificial intelligence), patients, medicine, data, and learning. Sentiment analysis revealed an overall majority of positive single word sentiments (e.g., intelligence, improve) with 230 positive and 172 negative sentiments with a total of 658 and 342 mentions of all positive and negative sentiments, respectively. Most frequently mentioned negative sentiments were cancer, risk, and bias. Most common bigrams identified by Markov chain depiction were related to analytical methods (e.g., label-free detection) and medical conditions/biological processes (e.g., rare circulating tumor cells). Conclusion: These results demonstrate the generated considerable interest of using #MedTwitterAI for promoting relevant content and engaging a broad and geographically diverse audience. The use of hashtags in Twitter-based campaigns can be an effective tool to raise awareness of interdisciplinary fields and enable knowledge-sharing on a global scale.

Research on Digital Technology Use in Cardiology: Bibliometric Analysis.

BACKGROUND: Digital technology uses in cardiology have become a popular research focus in recent years. However, there has been no published bibliometric report that analyzed the corresponding academic literature in order to derive key publishing trends and characteristics of this scientific area. OBJECTIVE: We used a bibliometric approach to identify and analyze the academic literature on digital technology uses in cardiology, and to unveil popular research topics, key authors, institutions, countries, and journals. We further captured the cardiovascular conditions and diagnostic tools most commonly investigated within this field. METHODS: The Web of Science electronic database was queried to identify relevant papers on digital technology uses in cardiology. Publication and citation data were acquired directly from the database. Complete bibliographic data were exported to VOSviewer, a dedicated bibliometric software package, and related to the semantic content of titles, abstracts, and keywords. A term map was constructed for findings visualization. RESULTS: The analysis was based on data from 12,529 papers. Of the top 5 most productive institutions, 4 were based in the United States. The United States was the most productive country (4224/12,529, 33.7%), followed by United Kingdom (1136/12,529, 9.1%), Germany (1067/12,529, 8.5%), China (682/12,529, 5.4%), and Italy (622/12,529, 5.0%). Cardiovascular diseases that had been frequently investigated included hypertension (152/12,529, 1.2%), atrial fibrillation (122/12,529, 1.0%), atherosclerosis (116/12,529, 0.9%), heart failure (106/12,529, 0.8%), and arterial stiffness (80/12,529, 0.6%). Recurring modalities were electrocardiography (170/12,529, 1.4%), angiography (127/12,529, 1.0%), echocardiography (127/12,529, 1.0%), digital subtraction angiography (111/12,529, 0.9%), and photoplethysmography (80/12,529, 0.6%). For a literature subset on smartphone apps and wearable devices, the Journal of Medical Internet Research (20/632, 3.2%) and other JMIR portfolio journals (51/632, 8.0%) were the major publishing venues. CONCLUSIONS: Digital technology uses in cardiology target physicians, patients, and the general public. Their functions range from assisting diagnosis, recording cardiovascular parameters, and patient education, to teaching laypersons about cardiopulmonary resuscitation. This field already has had a great impact in health care, and we anticipate continued growth.

Digital Teaching in Medical Education: Scientific Literature Landscape Review.

BACKGROUND: Digital teaching in medical education has grown in popularity in the recent years. However, to the best of our knowledge, no bibliometric report to date has been published that analyzes this important literature set to reveal prevailing topics and trends and their impacts reflected in citation counts. OBJECTIVE: We used a bibliometric approach to unveil and evaluate the scientific literature on digital teaching research in medical education, demonstrating recurring research topics, productive authors, research organizations, countries, and journals. We further aimed to discuss some of the topics and findings reported by specific highly cited works. METHODS: The Web of Science electronic database was searched to identify relevant papers on digital teaching research in medical education. Basic bibliographic data were obtained by the "Analyze" and "Create Citation Report" functions of the database. Complete bibliographic data were exported to VOSviewer for further analyses. Visualization maps were generated to display the recurring author keywords and terms mentioned in the titles and abstracts of the publications. RESULTS: The analysis was based on data from 3978 papers that were identified. The literature received worldwide contributions with the most productive countries being the United States and United Kingdom. Reviews were significantly more cited, but the citations between open access vs non-open access papers did not significantly differ. Some themes were cited more often, reflected by terms such as virtual reality, innovation, trial, effectiveness, and anatomy. Different aspects in medical education were experimented for digital teaching, such as gross anatomy education, histology, complementary medicine, medicinal chemistry, and basic life support. Some studies have shown that digital teaching could increase learning satisfaction, knowledge gain, and even cost-effectiveness. More studies were conducted on trainees than on undergraduate students. CONCLUSIONS: Digital teaching in medical education is expected to flourish in the future, especially during this era of COVID-19 pandemic.

Official Websites Providing Information on COVID-19 Vaccination: Readability and Content Analysis.

BACKGROUND: Online information on COVID-19 vaccination may influence people's perception and willingness to be vaccinated. Official websites of vaccination programs have not been systematically assessed before. OBJECTIVE: This study aims to assess and compare the readability and content quality of web-based information on COVID-19 vaccination posted on official/governmental websites. Furthermore, the relationship between evaluated website parameters and country vaccination rates were calculated. METHODS: By referring to an open data set hosted at Our World in Data, the 58 countries/regions with the highest total vaccination count as of July 8, 2021, were identified. Together with the websites from the World Health Organization and European Union, a total of 60 vaccination campaign websites were targeted. The "frequently asked questions" or "questions and answers" section of the websites were evaluated in terms of readability (Flesch Reading Ease score and Flesch-Kincaid Grade Level), quality (Health On the Net Foundation code [HONcode] certification and Quality Evaluation Scoring Tool), and content stating vaccination duration of protection and potential side effects. RESULTS: In terms of readability, the Flesch Reading Ease score of the vaccination frequently asked questions websites ranged between 11.2 and 69.5, with a mean of 40.9 (SD 13.2). Meanwhile, the Flesch-Kincaid Grade Level ranged between 6.5 and 17.6, with a mean of 12.1 (SD 2.8). In terms of quality, only 2 websites were HONcode certified, and the Quality Evaluation Scoring Tool score of the websites ranged between 7 and 20, with a mean of 15.3 (SD 3.1). Half of the websites (25/50) did not present a publication date or date of the last update. Regarding the duration of protection offered by the vaccines, 46% (23/50) of the websites stated that they do not know, and another 40% (20/50) did not address it. Five side effects of the vaccinations were most frequently mentioned, namely, fever/chill (41/50, 82%), various injection site discomfort events (eg, swelling, redness, or pain; 39/50, 78%), headache (36/50, 72%), fatigue (33/50, 66%), and muscle/joint pain (31/50, 62%). CONCLUSIONS: In general, the content quality of most of the evaluated websites was good, but HONcode certification should be considered, content should be written in a more readable manner, and a publication date or date of the last update should be presented.

Medical and Health-Related Misinformation on Social Media: Bibliometric Study of the Scientific Literature.

BACKGROUND: Social media has been extensively used for the communication of health-related information and consecutively for the potential spread of medical misinformation. Conventional systematic reviews have been published on this topic to identify original articles and to summarize their methodological approaches and themes. A bibliometric study could complement their findings, for instance, by evaluating the geographical distribution of the publications and determining if they were well cited and disseminated in high-impact journals. OBJECTIVE: The aim of this study was to perform a bibliometric analysis of the current literature to discover the prevalent trends and topics related to medical misinformation on social media. METHODS: The Web of Science Core Collection electronic database was accessed to identify relevant papers with the following search string: ALL=(misinformati* OR "wrong informati*" OR disinformati* OR "misleading informati*" OR "fake news*") AND ALL=(medic* OR illness* OR disease* OR health* OR pharma* OR drug* OR therap*) AND ALL=("social media*" OR Facebook* OR Twitter* OR Instagram* OR YouTube* OR Weibo* OR Whatsapp* OR Reddit* OR TikTok* OR WeChat*). Full records were exported to a bibliometric software, VOSviewer, to link bibliographic information with citation data. Term and keyword maps were created to illustrate recurring terms and keywords. RESULTS: Based on an analysis of 529 papers on medical and health-related misinformation on social media, we found that the most popularly investigated social media platforms were Twitter (n=90), YouTube (n=67), and Facebook (n=57). Articles targeting these 3 platforms had higher citations per paper (>13.7) than articles covering other social media platforms (Instagram, Weibo, WhatsApp, Reddit, and WeChat; citations per paper <8.7). Moreover, social media platform-specific papers accounted for 44.1% (233/529) of all identified publications. Investigations on these platforms had different foci. Twitter-based research explored cyberchondria and hypochondriasis, YouTube-based research explored tobacco smoking, and Facebook-based research studied vaccine hesitancy related to autism. COVID-19 was a common topic investigated across all platforms. Overall, the United States contributed to half of all identified papers, and 80% of the top 10 most productive institutions were based in this country. The identified papers were mostly published in journals of the categories public environmental and occupational health, communication, health care sciences services, medical informatics, and medicine general internal, with the top journal being the Journal of Medical Internet Research. CONCLUSIONS: There is a significant platform-specific topic preference for social media investigations on medical misinformation. With a large population of internet users from China, it may be reasonably expected that Weibo, WeChat, and TikTok (and its Chinese version Douyin) would be more investigated in future studies. Currently, these platforms present research gaps that leave their usage and information dissemination warranting further evaluation. Future studies should also include social platforms targeting non-English users to provide a wider global perspective.

Hybrid sterility genes in mice (Mus musculus): a peculiar case of PRDM9 incompatibility.

Hybrid sterility is a critical step in the evolution of reproductive barriers between diverging taxa during the process of speciation. Recent studies of young subspecies of the house mouse revealed a multigenic nature and frequent polymorphism of hybrid sterility genes as well as the recurrent engagement of the meiosis-specific gene PR domain-containing 9 (Prdm9) and X-linked loci. Prdm9-controlled hybrid sterility is essentially chromosomal in nature, conditioned by the sequence divergence between subspecies. Depending on the Prdm9 interallelic interactions and the X-linked Hstx2 locus, the same homologs either regularly recombine and synapse, or show impaired DNA DSB repair, asynapsis, and early meiotic arrest. Thus, Prdm9-dependent hybrid sterility points to incompatibilities affecting meiotic recombination as a possible mechanism of reproductive isolation between (sub)species.

Chromosome-wide characterization of meiotic noncrossovers (gene conversions) in mouse hybrids.

During meiosis, the recombination-initiating DNA double-strand breaks (DSBs) are repaired by crossovers or noncrossovers (gene conversions). While crossovers are easily detectable, noncrossover identification is hampered by the small size of their converted tracts and the necessity of sequence polymorphism. We report identification and characterization of a mouse chromosome-wide set of noncrossovers by next-generation sequencing of 10 mouse intersubspecific chromosome substitution strains. Based on 94 identified noncrossovers, we determined the mean length of a conversion tract to be 32 bp. The spatial chromosome-wide distribution of noncrossovers and crossovers significantly differed, although both sets overlapped the known hotspots of PRDM9-directed histone methylation and DNA DSBs, thus supporting their origin in the standard DSB repair pathway. A significant deficit of noncrossovers descending from asymmetric DSBs proved their proposed adverse effect on meiotic recombination and pointed to sister chromatids as an alternative template for their repair. The finding has implications for the molecular mechanism of hybrid sterility in mice from crosses between closely related Mus musculus musculus and Mus musculus domesticus subspecies.

Emerging Roles of PRDM Factors in Stem Cells and Neuronal System: Cofactor Dependent Regulation of PRDM3/16 and FOG1/2 (Novel PRDM Factors).

PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) (PR) homologous domain containing (PRDM) transcription factors are expressed in neuronal and stem cell systems, and they exert multiple functions in a spatiotemporal manner. Therefore, it is believed that PRDM factors cooperate with a number of protein partners to regulate a critical set of genes required for maintenance of stem cell self-renewal and differentiation through genetic and epigenetic mechanisms. In this review, we summarize recent findings about the expression of PRDM factors and function in stem cell and neuronal systems with a focus on cofactor-dependent regulation of PRDM3/16 and FOG1/2. We put special attention on summarizing the effects of the PRDM proteins interaction with chromatin modulators (NuRD complex and CtBPs) on the stem cell characteristic and neuronal differentiation. Although PRDM factors are known to possess intrinsic enzyme activity, our literature analysis suggests that cofactor-dependent regulation of PRDM3/16 and FOG1/2 is also one of the important mechanisms to orchestrate bidirectional target gene regulation. Therefore, determining stem cell and neuronal-specific cofactors will help better understanding of PRDM3/16 and FOG1/2-controlled stem cell maintenance and neuronal differentiation. Finally, we discuss the clinical aspect of these PRDM factors in different diseases including cancer. Overall, this review will help further sharpen our knowledge of the function of the PRDM3/16 and FOG1/2 with hopes to open new research fields related to these factors in stem cell biology and neuroscience.

Molecular Mechanisms Underlying Hepatocellular Carcinoma Induction by Aberrant NRF2 Activation-Mediated Transcription Networks: Interaction of NRF2-KEAP1 Controls the Fate of Hepatocarcinogenesis.

NF-E2-related factor 2 (NRF2) is a basic leucine zipper transcription factor, a master regulator of redox homeostasis regulating a variety of genes for antioxidant and detoxification enzymes. NRF2 was, therefore, initially thought to protect the liver from oxidative stress. Recent studies, however, have revealed that mutations in NRF2 cause aberrant accumulation of NRF2 in the nucleus and exert the upregulation of NRF2 target genes. Moreover, among all molecular changes in hepatocellular carcinoma (HCC), NRF2 activation has been revealed as a more prominent pathway contributing to the progression of precancerous lesions to malignancy. Nevertheless, how its activation leads to poor prognosis in HCC patients remains unclear. In this review, we provide an overview of how aberrant activation of NRF2 triggers HCC development. We also summarize the emerging roles of other NRF family members in liver cancer development.

Prdm9 Intersubspecific Interactions in Hybrid Male Sterility of House Mouse.

The classical definition posits hybrid sterility as a phenomenon when two parental taxa each of which is fertile produce a hybrid that is sterile. The first hybrid sterility gene in vertebrates, Prdm9, coding for a histone methyltransferase, was identified in crosses between two laboratory mouse strains derived from Mus mus musculus and M. m. domesticus subspecies. The unique function of PRDM9 protein in the initiation of meiotic recombination led to the discovery of the basic molecular mechanism of hybrid sterility in laboratory crosses. However, the role of this protein as a component of reproductive barrier outside the laboratory model remained unclear. Here, we show that the Prdm9 allelic incompatibilities represent the primary cause of reduced fertility in intersubspecific hybrids between M. m. musculus and M. m. domesticus including 16 musculus and domesticus wild-derived strains. Disruption of fertility phenotypes correlated with the rate of failure of synapsis between homologous chromosomes in meiosis I and with early meiotic arrest. All phenotypes were restored to normal when the domesticus Prdm9dom2 allele was substituted with the Prdm9dom2H humanized variant. To conclude, our data show for the first time the male infertility of wild-derived musculus and domesticus subspecies F1 hybrids controlled by Prdm9 as the major hybrid sterility gene. The impairment of fertility surrogates, testes weight and sperm count, correlated with increasing difficulties of meiotic synapsis of homologous chromosomes and with meiotic arrest, which we suppose reflect the increasing asymmetry of PRDM9-dependent DNA double-strand breaks.

Ethnopharmacological Applications Targeting Alcohol Abuse: Overview and Outlook.

Excessive alcohol consumption is the cause of several diseases and thus is of a major concern for society. Worldwide alcohol consumption has increased by many folds over the past decades. This urgently calls for intervention and relapse counteract measures. Modern pharmacological solutions induce complete alcohol self-restraint and prevent relapse, but they have many side effects. Natural products are most promising as they cause fewer adverse effects. Here we discuss in detail the medicinal plants used in various traditional/folklore medicine systems for targeting alcohol abuse. We also comprehensively describe preclinical and clinical studies done on some of these plants along with the possible mechanisms of action.

Corrigendum: Ethnopharmacological Approaches for Therapy of Jaundice: Part II. Highly Used Plant Species from Acanthaceae, Euphorbiaceae, Asteraceae, Combretaceae, and Fabaceae Families.

[This corrects the article on p. 519 in vol. 8, PMID: 28848436.].