Natural genetic engineering: A programmed chromosome/DNA elimination.

Typically, all cells of a given organism have the same set of chromosomes. However, there are exceptions to this rule, and in many organisms, the somatic cells and germ cells, various types of somatic cells or organs, or females and males, have different genomes. One of the sources of such differences is chromosome/DNA elimination/chromatin diminution that is a naturally programmed phenomenon. We describe chromosome/DNA elimination in various organisms and present the current hypotheses on its origin, mechanisms, significance, and consequences.

Coordination of floral and fiber development in cotton (Gossypium) by hormone- and flavonoid-signalling associated regulatory miRNAs.

Various plant development activities and stress responses are tightly regulated by various microRNAs (miRNA) and their target genes, or transcription factors in a spatiotemporal manner. Here, to exemplify how flowering-associated regulatory miRNAs synchronize their expression dynamics during floral and fiber development in cotton, constitutive expression diminution transgenic lines of auxin-signaling regulatory Gh-miR167 (35S-MIM167) were developed through target mimicry approach. 'Moderate' (58% to 80%)- and 'high' (> 80%)-Gh-miR167 diminution mimic lines showed dosage-dependent developmental deformities in anther development, pollen maturation, and fruit (= boll) formation. Cross pollination of 'moderate' 35S-MIM167 mimic lines with wild type (WT) plant partially restored boll formation and emergence of fiber initials on the ovule surface. Gh-miR167 diminution favored organ-specific transcription biases in miR159, miR166 as well as miR160, miR164, and miR172 along with their target genes during anther and petal development, respectively. Similarly, accumulative effect of percent Gh-miR167 diminution, cross regulation of its target ARF6/8 genes, and temporal mis-expression of hormone signaling- and flavonoid biosynthesis-associated regulatory miRNAs at early fiber initiation stage caused irregular fiber formation. Spatial and temporal transcription proportions of regulatory miRNAs were also found crucial for the execution of hormone- and flavonoid-dependent progression of floral and fiber development. These observations discover how assorted regulatory genetic circuits get organized in response to Gh-miR167 diminution and converge upon ensuing episodes of floral and fiber development in cotton.

Proportion of diabetic retinopathy among diabetics presenting for the first time to a tertiary eye institute in South India.

PURPOSE: To detect the proportion of diabetic retinopathy (DR) among diabetics visiting a tertiary eye care institute and correlate presenting symptoms to clinical diagnosis. METHODS: The study recruited 1000 eyes of 1000 diabetics visiting a tertiary eye care institute in South India for the first time. Along with basic demographic data and systemic history, details of presenting complaints and clinical diagnosis were noted. RESULTS: Data from 956 cases were analyzed. There were 29 (3%) newly diagnosed diabetics and 927 (97%) known diabetics. The commonest reason for the hospital visit was diminution of vision (66%) followed by "visiting for a routine checkup" (22.3%). Diabetic retinopathy was seen in 492 (51.5%), cataract in 161(17%) and refractive error in 240 patients (79.2%). Vision-threatening DR was present in 216 cases (22.59%) and clinically significant macular edema in 73 cases (7.63%) at first presentation itself. CONCLUSION: The cohort from a tertiary eye care institute has higher proportion of diabetic retinopathy, with vision-threatening DR at presentation. These data emphasize the need for more robust screening for DR, along with population awareness programs.

[Relevancy and efficacy of advanced nursing practice in private practice to promote smoking cessation]. / Pertinence et efficacité d'une pratique infirmière avancée en libéral dans le sevrage tabagique.

Raising awareness of the harmful effects of smoking on health and supporting smokers who wish to quit are important public health challenges. The involvement of nurses in these specific healthcare actions targeting the motivation to change seems to be a promising approach as revealed by a study summarised in this article.

Chromatin Diminution in Cyclops kolensis Lill. (Copepoda, Crustacea) as a Radical Way to Inactivate Redundant Genome in Somatic Cells.

Chromatin diminution (CD) is a phenomenon of programmed DNA elimination which takes place in early embryogenesis in some eukaryotes. The mechanism and biological role of CD remain largely unknown. During CD in the freshwater copepod Cyclops kolensis, the genome of cells of the somatic lineage is reorganized and reduced in size by more than 90% without affecting the genome of germline cells. Although the diploid chromosome number is unchanged, chromosome size is dramatically reduced by CD. The eliminated DNA consists primarily of repetitive sequences and localizes within granules during the elimination process. In this review, we provide an overview of CD in C. kolensis including both cytological and molecular studies.

Activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction.

Recent evidence indicate that melanotan II (MTII) reduces body mass independently of caloric reduction. Because MTII induces a transient hypophagia, caloric reduction is still considered a primary mechanism for MTII-mediated body mass loss. To examine the contribution of caloric reduction to long-term body mass loss in response to MTII, we centrally infused MTII or vehicle in ad libitum fed (MTII and Control) animals in comparison with a group of animals that were pair-fed (PF) to the MTII group. Food intake and body mass were recorded daily, and body composition was assessed biweekly. The present study demonstrates that central MTII-mediated body mass loss is only partially mediated by caloric restriction, and the long-term body mass loss is independent of the initial hypophagia. More importantly, central MTII administration induced a rapid but sustained fat mass loss, independently of caloric reduction. MTII-treated animals preserved their lean/fat mass ratio throughout the study, whereas PF animals underwent a transient reduction of lean/fat mass ratio that was only normalized when food intake returned to Control level. In summary, it can be concluded that activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction.

Strawberry (cv. Romina) Methanolic Extract and Anthocyanin-Enriched Fraction Improve Lipid Profile and Antioxidant Status in HepG2 Cells.

Dyslipidemia and oxidation of low density lipoproteins (LDL) are recognized as critical factors in the development of atherosclerosis. Healthy dietary patterns, with abundant fruit and vegetable consumption, may prevent the onset of these risk factors due to the presence of phytochemical compounds. Strawberries are known for their high content of polyphenols; among them, flavonoids are the major constituents, and it is presumed that they are responsible for the biological activity of the fruit. Nevertheless, there are only a few studies that actually evaluate the effects of different fractions isolated from strawberries. In order to assess the effects of two different strawberry extracts (whole methanolic extract/anthocyanin-enriched fraction) on the lipid profile and antioxidant status in human hepatocellular carcinoma (HepG2) cells, the triglycerides and LDL-cholesterol content, lipid peroxidation, intracellular reactive oxygen species (ROS) content and antioxidant enzymes' activity on cell lysates were determined. Results demonstrated that both strawberry extracts not only improved the lipid metabolism by decreasing triglycerides and LDL-cholesterol contents, but also improved the redox state of HepG2 cells by modulating thiobarbituric acid-reactive substances production, antioxidant enzyme activity and ROS generation. The observed effects were more pronounced for the anthocyanin-enriched fraction.

[Facelift under local anesthaesia in outpatient surgery]. / Le lifting du visage sous anesthésie locale en ambulatoire.

Facelift under local anesthesia: the author recounts his experience and methodology developed to operate facelift under local anesthesia in order to reduce operative morbidity and be able to operate persons who do not desire general anesthesia. The technique is based on the knowledge of the sensitive anatomy of the face as well as the practice of sensitive conduction blocks at the level of the face allowing to decrease the doses of local anesthetics.

EMBRYONIC DEVELOPMENT AND A QUANTITATIVE MODEL OF PROGRAMMED DNA ELIMINATION IN MESOCYCLOPS EDAX (S. A. FORBES, 1891) (COPEPODA: CYCLOPOIDA).

The highly programmed fragmentation of chromosomes and elimination of large amounts of nuclear DNA from the presomatic cell lineages (i.e., chromatin diminution), occurs in the embryos of the freshwater zooplankton Mesocyclops edax (S. A. Forbes, 1891) (Crustacea: Copepoda). The somatic genome is reorganized and reduced to a size five times smaller even though the germline genome remains intact. We present the first comprehensive, quantitative model of DNA content throughout embryogenesis in a copepod that possesses embryonic DNA elimination. We used densitometric image analysis to measure the DNA content of polar bodies, germline and somatic nuclei, and excised DNA "droplets." We report: 1) variable DNA contents of polar bodies, some of which do not contain the amount corresponding to the haploid germline genome size; 2) presence of pronuclei in newly laid embryo sacs; 3) gonomeric chromosomes in the second to fourth cleavage divisions and in the primordial germ cell and primordial endoderm cell during the fifth cleavage division; 4) timing of early embryonic cell stages, elimination of DNA, and divisions of the primordial germ cell and primordial endoderm cell at 22°C; and 5) persistence of a portion of the excised DNA "droplets" throughout embryogenesis. DNA elimination is a trait that spans multiple embryonic stages and a knowledge of the timing and variability of the associated cytological events with DNA elimination will promote the study of the molecular mechanisms involved in this trait. We propose the "genome yolk hypothesis" as a functional explanation for the persistence of the eliminated DNA that might serve as a resource during postdiminution cleavage divisions.

Optic Neuritis in Resolving Phase of COVID-19 Infection and Its Management: A Case Report.

Optic neuritis is assumed to be immune-mediated, although the specific antigens that cause demyelination are uncertain. Systemic T-cell activation is detected at the onset of symptoms, which occurs before alterations in cerebrospinal fluid (CSF). The optic nerve disease is a rare disease and can occur in one or both eyes, especially in those with no established inflammatory or autoimmune illnesses. Adult ophthalmic neuritis is usually unilateral and is frequently associated with multiple sclerosis (MS). Generally, it starts as a rapid loss of vision and pain in eye movement. It progresses and achieves the maximal deficiency over a week. The objectives of this paper were to determine the association between coronavirus disease 2019 (COVID-19) and optic neuritis and to study the management of optic neuritis in the resolving phase of COVID-19. A case study was done on a 38-year-old female complaining of sudden diminution of vision in her right eye for one week. She tested positive on the reverse transcriptase-polymerase chain reaction (RT-PCR) test for COVID-19 for which she was managed symptomatically and was started on antiretrovirals. This case report is based on an infrequent COVID-19 complication. It has been proposed that this virus has the probability of manifesting various neurological complications. In our case, optic neuritis occurs mainly three weeks after COVID-19 infection. Our patient was managed by intravenous methylprednisolone injection followed by oral prednisone for 14 days. So, further case studies will be required to support the above treatment plan for optic neuritis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unilateral or bilateral optic neuritis can occur as a neurological complication in the resolving stage of COVID-19 infection. Early detection and treatment with steroids can result in the best visual outcome.

MDCTA diagnosis of cerebral vessel disease among patients with arterial hypertension.

BACKGROUND: to study changes involving cerebral vessels in patients with hypertension and various levels of total cardiovascular risk. MATERIAL/METHODS: One hundred and thirty-four patients underwent CT-angiography of intracranial vessels. Ninety-eight of them were diagnosed with hypertension. Taking into consideration high blood pressure, presence of risk factors and target organ damage subjects were divided into 4 groups: with low, medium, high and very high total cardiovascular risk. Control group included 36 patients. They were not diagnosed with hypertension at the time of examination. One hundred and five patients were examined using a 4-slice CT scanner (Toshiba Asteion 4, Toshiba Medical System, Japan), and 29 patients were examined using a 128-slice scanner (Siemens Definition AS+, Siemens Healthcare, Germany) with an injection system. We used iodine-containing contrast agents such as iodixanol and iopromide for angiography. RESULTS: Anatomical and topographic changes of cerebral vessels were most frequently found in hypertensive patients with high and very high total cardiovascular risk. Narrowing of vertebral vessels was the most common change (27 patients (27.55%), 21 patients (21.43%) had narrowing of the right artery, and 6 (6.12%) subjects - of the left one). Tortuous course of internal carotid arteries at the neck level was visualized in 11 patients (11.22%). Narrowing of A1 segment of anterior cerebral artery was noted in 9 patients (9.18%), of the right one - in 8 patients (8.16%), of the left one - in 1 patient (1.02%). Aneurysmal dilation of intracranial vessels was visualized in 6 patients (6.12%). Saccular aneurysm of left internal carotid artery was diagnosed in 2 patients (2.04%), one patient (1.02%) had right internal carotid artery aneurysm and one patient (1.02%) had an aneurysm of the basilar artery. DISCUSSIONS: the most common changes of cerebral vessels diagnosed in MDCTA among patients with hypertension included various degrees of narrowing of vertebral vessels, anterior, posterior and posterior communicating arteries and internal carotid arteries. Changes of middle cerebral arteries and basilar arteries were extremely rare, thus we can say that these vessels are influenced by high blood pressure to lesser extent. We established the relationship between changes in cerebral blood vessels and total cardiovascular risk. Therefore, we believe that findings will be useful for establishing prognosis in hypertension and prevention of complications such as stroke. CONCLUSIONS: MDCT angiography is a highly informative method to study changes of cerebral vessels in patients with hypertension. The relationship between changes in cerebral blood vessels diagnosed through MDCT angiography and the level of total cardiovascular risk among patients with hypertension had been established.

An improved germline genome assembly for the sea lamprey Petromyzon marinus illuminates the evolution of germline-specific chromosomes.

Programmed DNA loss is a gene silencing mechanism that is employed by several vertebrate and nonvertebrate lineages, including all living jawless vertebrates and songbirds. Reconstructing the evolution of somatically eliminated (germline-specific) sequences in these species has proven challenging due to a high content of repeats and gene duplications in eliminated sequences and a corresponding lack of highly accurate and contiguous assemblies for these regions. Here, we present an improved assembly of the sea lamprey (Petromyzon marinus) genome that was generated using recently standardized methods that increase the contiguity and accuracy of vertebrate genome assemblies. This assembly resolves highly contiguous, somatically retained chromosomes and at least one germline-specific chromosome, permitting new analyses that reconstruct the timing, mode, and repercussions of recruitment of genes to the germline-specific fraction. These analyses reveal major roles of interchromosomal segmental duplication, intrachromosomal duplication, and positive selection for germline functions in the long-term evolution of germline-specific chromosomes.

[Predictive factors of spontaneous pregnancies among women with diminished ovarian reserve patients treated with DHEA]. / Facteurs prédictifs de grossesse spontanée chez les femmes présentant une réserve ovarienne diminuée traitées par DHEA.

INTRODUCTION: Diminished ovarian reserve remains a challenge in the reproductive medicine field. Treatment options for these patients are limited and there is no consensus to make any recommendations. Regarding adjuvant supplements, DHEA could play a role in follicular recruitment and, therefore, may increase spontaneous pregnancy rate. MATERIALS AND METHODS: This study was a monocentric historical and observational cohort study carried out in the reproductive medicine department at the University Hospital, Femme-Mère-Enfant in Lyon. All women presenting with a diminished ovarian reserve treated with 75mg/day of DHEA were consecutively included. The main objective was to evaluate the spontaneous pregnancy rate. The secondary objectives were to identify predictive factors for pregnancy and the evaluation of treatment side effects. RESULTS: Four hundred and thirty-nine women were included. In all, 277 were analyzed, 59 had a spontaneous pregnancy (21.3%). The probability of being pregnant was respectively 13.2% (IC95 9-17.2%), 21.3% (IC95 15.1-27%) and 38.8% (IC95 29.3-48.4%) at 6, 12 and 24 months. Only 20.6% of patients complained of side effects. CONCLUSION: DHEA may improve spontaneous pregnancies in women with diminished ovarian reserve without any stimulation.

Insights on the carbon footprint of radiotherapy in France.

The French healthcare system is responsible for 8% of the national footprint. Achieving a net zero emissions scenario will require a 4-5 fold decrease of carbon emissions in the coming years. The carbon footprint of radiation therapy has not been specifically studied to date. In this review we summarize the content of the carbon footprint dedicated session at the annual meeting of the French society of radiation oncology (SFRO). We discuss the French healthcare system carbon footprint and its major drivers and our work on the estimation of the carbon footprint of external beam radiation therapy in the French setting. We developed a dedicated methodology to estimate the carbon footprint related to radiation therapies, and describe the main drivers of emissions based on a single centre as an example, namely patient's rides, accelerators acquisition and maintenance and data storage. Based on the carbon footprint calculated in our centres, we propose mitigation strategies and an estimation of their respective potential. Our results may be extrapolated to other occidental settings by adapting emission factors (kilograms of carbon per item or euro) to other national settings. External beam radiation therapy has a major carbon footprint that may be mitigated in many ways that may impact how radiation therapy treatments are delivered, as well as the national organization of the radiotherapy sector. This needs to be taken into account when thinking about the future of radiotherapy.

[Functional Heart Complaints]. / Funktionelle Herzbeschwerden.

Functional Heart Complaints Abstract. Functional complaints often manifest as cardiac symptoms (palpitations, thoracic complaints, reduced performance, dyspnea). Prognostically relevant clinical situations must be identified or excluded through targeted diagnostics. In the absence of prognostically relevant diseases action is wanted only in the case of subjective suffering, which is significantly influenced by the patient's emotional processing of the experience. Various therapy options can be used to treat functional heart complaints (do nothing/ignore symptoms, optimal treatment of any underlying diseases, phytotherapy, antiarrhythmic drugs, interventional therapy, physical training, psychocardiological treatment, resilience strengthening etc.).

Stress-Induced Changes in Effective Connectivity During Regulation of the Emotional Response to Threat.

Background: Stress-related disruption of emotion regulation appears to involve the prefrontal cortex (PFC) and amygdala. However, the interactions between brain regions that mediate stress-induced changes in emotion regulation remain unclear. The present study builds upon prior work that assessed stress-induced changes in the neurobehavioral response to threat by investigating effective connectivity between these brain regions. Methods: Participants completed the Montreal Imaging Stress Task followed by a Pavlovian fear conditioning procedure during functional magnetic resonance imaging. Stress ratings and psychophysiological responses were used to assess stress reactivity. Effective connectivity during fear conditioning was identified using multivariate autoregressive modeling. Effective connectivity values were calculated during threat presentations that were either predictable (preceded by a warning cue) or unpredictable (no warning cue). Results: A neural hub within the dorsomedial PFC (dmPFC) showed greater effective connectivity to other PFC regions, inferior parietal lobule, insula, and amygdala during predictable than unpredictable threat. The dmPFC also showed greater connectivity to different dorsolateral PFC and amygdala regions during unpredictable than predictable threat. Stress ratings varied with connectivity differences from the dmPFC to the amygdala. Connectivity from dmPFC to amygdala was greater in general during unpredictable than predictable threat, however, this connectivity increased during predictable compared with unpredictable threat as stress reactivity increased. Conclusions: Our findings suggest that acute stress disrupts connectivity underlying top-down emotion regulation of the threat response. Furthermore, increased connectivity between the dmPFC and amygdala may play a critical role in stress-induced changes in the emotional response to threat. Impact statement The present study builds upon prior work that assessed stress-induced changes in the human neurobehavioral response to threat by demonstrating that increased top-down connectivity from the dorsomedial prefrontal cortex to the amygdala varies with individual differences in stress reactivity. These findings provide novel evidence in humans of stress-induced disruption of a specific top-down corticolimbic circuit during active emotion regulation processes, which may play a causal role in the long-term effects of chronic or excessive stress exposure.

Delete and survive: strategies of programmed genetic material elimination in eukaryotes.

Genome stability is a crucial feature of eukaryotic organisms because its alteration drastically affects the normal development and survival of cells and the organism as a whole. Nevertheless, some organisms can selectively eliminate part of their genomes from certain cell types during specific stages of ontogenesis. This review aims to describe the phenomenon of programmed DNA elimination, which includes chromatin diminution (together with programmed genome rearrangement or DNA rearrangements), B and sex chromosome elimination, paternal genome elimination, parasitically induced genome elimination, and genome elimination in animal and plant hybrids. During programmed DNA elimination, individual chromosomal fragments, whole chromosomes, and even entire parental genomes can be selectively removed. Programmed DNA elimination occurs independently in different organisms, ranging from ciliate protozoa to mammals. Depending on the sequences destined for exclusion, programmed DNA elimination may serve as a radical mechanism of dosage compensation and inactivation of unnecessary or dangerous genetic entities. In hybrids, genome elimination results from competition between parental genomes. Despite the different consequences of DNA elimination, all genetic material destined for elimination must be first recognised, epigenetically marked, separated, and then removed and degraded.

A Rare Case of Orbital Adenoid Cystic Carcinoma Mimicking as Optic Nerve Glioma.

Adenoid cystic carcinoma is an uncommon epithelial cell tumour that usually originates from glands. They arise from the upper respiratory tract, lungs, mammary glands, and skin, but most commonly from the salivary glands and lacrimal glands. Our article reports a 53-year-old individual presenting with a history of diminution of visual acuity over the past one and a half months, also associated with a right-sided headache and throbbing eye pain not relieved by medication. Examination revealed right axial proptosis, ptosis, and visual acuity of 6/36, right afferent pupillary defect (RAPD), restriction of ocular movements in supraduction, dextroelevation, and abduction. The fellow eye was completely normal. MRI revealed an enhancing lesion in the retrobulbar area of the right orbit indicative of optic nerve glioma of stage 2. The patient underwent orbito-zygomatic craniotomy with subtotal excision of the mass by a neurosurgeon. Following surgery, histopathological examination of the excised tumour revealed features consistent with adenoid cystic carcinoma. On the third post-operative day, the subject's vision improved to counting fingers at 3 metres, and extraocular movements were regained.

New Perspectives on the Evolution of Within-Individual Genome Variation and Germline/Soma Distinction.

Genomes can vary significantly even within the same individual. The underlying mechanisms are manifold, ranging from somatic mutation and recombination, development-associated ploidy changes and genetic bottlenecks, over to programmed DNA elimination during germline/soma differentiation. In this perspective piece, we briefly review recent developments in the study of within-individual genome variation in eukaryotes and prokaryotes. We highlight a Society for Molecular Biology and Evolution 2020 virtual symposium entitled "Within-individual genome variation and germline/soma distinction" and the present Special Section of the same name in Genome Biology and Evolution, together fostering cross-taxon synergies in the field to identify and tackle key open questions in the understanding of within-individual genome variation.

Fascinating Chemopreventive Story of Wogonin: A Chance to Hit on the Head in Cancer Treatment.

Cancer, global havoc, is a group of debilitating diseases that strikes family as well as society. Cancer cases are drastically increasing these days. Despite many therapies and surgical procedures available, cancer is still difficult to control due to limited effective therapies or targeted therapies. Natural products can produce lesser side effects to the normal cells, which are the major demerit of chemotherapies and radiation. Wogonin, a natural product extracted from the plant, Scutellaria baicalensis has been widely studied and found with a high caliber to tackle most of the cancers via several mechanisms that include intrinsic as well as extrinsic apoptosis signaling pathways, carcinogenesis diminution, telomerase activity inhibition, metastasis inhibition in the inflammatory microenvironment, anti-angiogenesis, cell growth inhibition and arrest of the cell cycle, increased generation of H2O2 and accumulation of Ca2+ and also as an adjuvant along with anticancer drugs. This article discusses the role of wogonin in various cancers, its synergism with various drugs, and the mechanism by which wogonin controls tumor growth.