Temporal Dissection Research Articles

A New Multiplane Dissection Method for Frontotemporal Lift and Fixation.

Lifting procedures of the upper face have gained significant popularity, and various methods and dissection planes have been described. The deep temporalis fascia (DTF) is a crucial structure for securing lifting sutures and allowing horizontal tissue vectorization. However, achieving vertical eyebrow lifting often requires bone maneuvers and introduces potential complications. This letter proposes a novel multiplanar dissection method for the temporal and forehead regions, obviating the need for bone maneuvers in lifting suture fixations. The presence of the subgaleal fascia in the temporal region has been identified, in addition to the DTF and superficial temporal fascia. Furthermore the superficial temporal fascia is divided into 3 layers, with attention paid to their medial connection with the structures of the forehead. Surgical techniques involve meticulous dissection down to the DTF and identification of the subgaleal fascia for lateral temporal dissection or transition to the subplane of the epicranial aponeurosis for forehead lifting. By leaving a thick layer, the subplane of the epicranial aponeurosis during forehead lifting eliminates the need for drilling and reduces the risk of relapse. The described multiplanar dissection method enhances the safety and effectiveness of forehead lift procedures, offers a viable alternative to bone drilling, minimizes flap-related complications, and provides valuable insights for facial rejuvenation surgery.

A new 3D-printed temporal bone: ‘the SAPIENS’—specific anatomical printed-3D-model in education and new surgical simulations

PurposeOtology and neuro-otology surgeries pose significant challenges due to the intricate and variable anatomy of the temporal bone (TB), requiring extensive training. In the last years 3D-printed temporal bone models for otological dissection are becoming increasingly popular. In this study, we presented a new 3D-printed temporal bone model named 'SAPIENS', tailored for educational and surgical simulation purposes.MethodsThe 'SAPIENS' model was a collaborative effort involving a multidisciplinary team, including radiologists, software engineers, ENT specialists, and 3D-printing experts. The development process spanned from June 2022 to October 2023 at the Department of Sense Organs, Sapienza University of Rome.Acquisition of human temporal bone images; temporal bone rendering; 3D-printing; post-printing phase; 3D-printed temporal bone model dissection and validation.ResultsThe 'SAPIENS' 3D-printed temporal bone model demonstrated a high level of anatomical accuracy, resembling the human temporal bone in both middle and inner ear anatomy. The questionnaire-based assessment by five experienced ENT surgeons yielded an average total score of 49.4 ± 1.8 out of 61, indicating a model highly similar to the human TB for both anatomy and dissection. Specific areas of excellence included external contour, sigmoid sinus contour, cortical mastoidectomy simulation, and its utility as a surgical practice simulator.ConclusionWe have designed and developed a 3D model of the temporal bone that closely resembles the human temporal bone. This model enables the surgical dissection of the middle ear and mastoid with an excellent degree of similarity to the dissection performed on cadaveric temporal bones.

A temporal dissection of late Quaternary volcanism and related hazards within the Rio Grande rift and along the Jemez lineament of New Mexico, USA

Abstract New 40Ar/39Ar ages, combined with selected ages from published studies, provide detailed insight into the late Quaternary (<500 ka) eruptive history and related hazards of the Rio Grande rift and Jemez lineament of New Mexico, USA. Most eruptions in the region during this time were within monogenetic volcanic fields, which largely produced cinder cones and mafic lava flows. 40Ar/39Ar ages of mafic groundmass determined using the high-sensitivity ARGUS VI multicollector mass spectrometer are significantly more precise, by as much as an order of magnitude, than prior 40Ar/39Ar dates. The high-precision data permit more rigorous interpretation of age spectra and isochrons, leading to a greater confidence in assigning eruption ages, and thus allowing more accurate and thorough calculations of eruptive rates and repose periods. For most fields, comprehensive dating identifies a greater number of late Quaternary eruptions than previously known and, for some fields, determines younger-than-previously established ages for the last eruptive events. Repose periods in the fields range from too short to measure with the 40Ar/39Ar method to a few hundred thousand years, which suggests that all 12 fields in the rift and lineament with late Quaternary activity should be considered dormant rather than extinct, with the possibility of future eruptions. Average recurrence intervals for these fields during the late Quaternary range from 16.5 k.y. to 170.8 k.y. Many fields display peak periods of activity where rates spike to a recurrence interval of 5 k.y. or less. At the scale of the entire rift and lineament, 75 late Quaternary eruptions were dated, yielding an average recurrence interval of 6.5 k.y., which is a minimum estimate considering the likelihood of undated eruptions (either not studied or buried). During the last 100 k.y., the volcanic record is better preserved, and the recurrence interval is 3.2 k.y., which indicates that the current hiatus of 3.9 ± 1.2 k.y. is typical for the region. Since ca. 36 ka, the average recurrence interval decreased to 2.3 k.y., which suggests a slight increase in recent activity. When ages are compared to vent locations, a previously unrecognized migrational pattern is observed in nearly all of the fields studied. Migration vectors vary from 1.0 cm/yr to 4.0 cm/yr, and always with an eastward component—similar to migration patterns at some other late Cenozoic fields throughout the American Southwest. Volcanic migration is attributed to a combination of mechanisms including asthenospheric convection along the margin of the Colorado Plateau, North American plate motion over partial mantle melt, and extensional tectonics. Developing similar high-precision chronologies for other Quaternary fields throughout southwestern North America will be necessary to better understand the volcanic hazards of the region.

Novel Hybrid Technique for Preservation of Frontal Branch of Facial Nerve: Subgaleal Preinterfascial Dissection

The pterional approach is the workhorse of skull-base neurosurgery, which allows virtual access to any intracranial lesion around the circle of Willis. Preserving the frontotemporal branch of the facial nerve and conserving the temporal muscle's symmetry are fundamental objectives besides the access that can be obtained through this versatile neurosurgical technique. This manuscript proposes a subgaleal preinterfascial dissection, a novel hybrid technique that provides advantages of previously described temporal muscle dissection techniques while preserving the integrity of facial nerve branches and the unobstructed broad pterional region. We describe the subgaleal preinterfascial dissection as a safe and simple to technique to achieve preservation of the facial nerve frontal branches during anterolateral approaches. Two cadaveric heads were skillfully dissected and studied to perform a proper subgaleal preinterfascial dissection on both sides of each cadaver. Afterward, the same technique was employed in 108 patients during a pterional approach for different neurosurgical diseases, with a postoperative follow-up of 6 months. None of the 108 patients presented postoperative frontotemporal branch palsy during postoperative follow-up. Likewise, no complications related to the proposed technique were present. The subgaleal preinterfascial dissection is a reliable, safe technique that may be employed during a pterional approach with an unobstructed surgical view and excellent cosmetic and functional results, preserving the frontotemporal branch of the facial nerve.

A data-driven analysis of the aviation recovery from the COVID-19 pandemic

In Summer 2022, after a lean COVID-19 spell of almost three years, many airlines reported profits and some airlines even outperformed their pre-pandemic records. In context of the perceived recovery, it is interesting to understand how different markets have gone through the pandemic challenges. In this study, we perform a spatial and temporal dissection of the recovery process the global aviation system went through since May 2020. At the heart of this study, we investigate the patterns underlying market entry decisions during the recovery phase. We identify a rather heterogeneous type of recovery as well as its underlying drivers. We believe that our work is a timely contribution to the research on COVID-19 and aviation, complementary to the existing studies in the literature.

Evolution tumour models paving the way for understanding oral carcinogenesis.

Throughout the centuries, the world's outstanding scientists and research groups have gathered their efforts to characterise the initiation and progression of malignant neoplasms. The temporal dissection of tumourigenesis provided by phylogenetic studies is one of the milestones in understanding cancer; however, some black boxes are still unsolved. Currently, there is no consensus regarding the development of oral squamous cell carcinoma (OSCC), the leading cancer of the head and neck region. Oral epithelial dysplasia (OED) may precede oral cancer and, occasionally, be clinically evident as white, red or mixed mucosal lesions, called oral potentially malignant disorders (OPMD). In a stepwise view of oral carcinogenesis, OED and OPMD have been considered harbingers of oral cancer. Nevertheless, the malignant transformation of OPMD is a rare event. Most of these disorders remain benign and can even regress, making it challenging to formulate evolutionary hypotheses for OSCC initiation. Deciphering OED evolution is vital to highlight the potential drivers of oral carcinogenesis and molecular targets for OSCC preventative and therapeutic strategies. This narrative review synthesises the main concepts of evolutionary theories and discusses which of them better explains OED development and malignant transformation.

A Cadaveric Study of Anatomical and Radiological Correlation of Mastoid Air Cells System in Relation to its Morphology.

A cadaveric study to know the anatomical and radiological correlation between the mastoid air cell system in relation to its volume and morphology. This is a rare and one of its kind of cadaveric study on temporal bone in which comparison of pre dissection and post cortical mastoidectomy dissection on x-ray mastoid in relation to their dimensions. To study the anatomical and radiological correlation of mastoid air cell system in relation to its morphology using pre and post dissection x-ray measurements and dissection method. 30 adult cadaveric, temporal bone cortical mastoidectomy dissections were performed and X-ray mastoid with a pre and post mastoid dissection measurements using vernier caliper was done. Further 3-D analysis of volume of mastoid cavity compared with a post dissection digital radiographic measurements was carried out. On statistical analysis, mean surface area of MACS, shortest length between sigmoidsinus and posterior wall of EAC, also shortest distance between dural plate and mastoid tip, in pre and post dissection x-ray mastoid and in direct mastoid cavity measurements were not found to be significant. Mastoidectomy being the treatment of choice in day to day practise in many cases this study hopes to add up to the present understanding for the MACS dynamics and assesses the possible anatomical variations that can exist. This study helps us to find the approximate time required for surgery to perform cortical mastoidectomy.

Drones and Dendro: a strategic technological development link for forest monitoring

Forests are a matter of national interest and represent a strategic resource for society. However, forests face challenges that deserveto be addressed with state-of-the-art technologies. Climate change, in particular, has led to changes in the structure andbiogeography of forest stands. Based on a literature review, the lessons learned by the DendroRed research group(https://dendrored.ujed.mx/) over the last five years are highlighted here. First, it is proved that growth rings are reliable sources ofecological processes faced by trees. Their temporal dissection has refined the understanding of climate responses, as well as theirpotential to reconstruct carbon stocks at tree level. The integration of these natural records with remote sensing techniques haselucidated the seasonal modification of climate. Unmanned aerial vehicle (UAV) monitoring offers a spatial and spectralperspective usually ignored, but with great potential in forest monitoring. We document the benefits in estimating aerial attributesof the canopy, as well as indices on foliar dynamics and mention areas of opportunity. All this knowledge can be integrated into atechnological package for monitoring forest resources and has impacts on forest productivity. However, it deserves additionalefforts to influence forest management policies.

Endoscopic diving technique for hearing preservation in managing labyrinth-invading cholesteatomas.

Complete removal of the matrix over the existing fistula in the event of an extensive cholesteatoma with labyrinth invasion can result in total deafness. This study aimed to present a novel method of underwater endoscopic labyrinth dissection using continuous steroid irrigation (CSI) and systemic steroid administration for hearing preservation. The endoscopic diving technique (EDT) was used to dissect semicircular canals, revealing the underwater anatomy of membranous labyrinth structures, in two cadaver temporal bones. EDT with CSI was used in three clinical cases with extensive cholesteatoma. On cadaver temporal bones, the anatomy of the lateral (LSC), superior (SSC), and posterior membranous semicircular canals with their respective ampullas and common crus was documented. In the first case managed with transcanal EDT, the LSC was eroded across almost its entire length. The fallopian canal was circumferentially eroded at the second genu and part of the mastoid segment. The cholesteatoma matrix was completely removed, and the membranous LSC was preserved. In the second and third cases, we were able to remove the cholesteatoma matrix along the eroded bony semicircular canals while keeping the membranes intact. No sensorineural hearing loss was detected in the postoperative masked pure-tone audiometry at a mean follow-up time of 12months or cholesteatoma recurrence at the follow-up imaging. EDT with CSI can be safely utilized in the course of temporal bone labyrinth dissections and provides advantages during cholesteatoma removal over the eroded labyrinth on preservation of the membranous structures, and thus may help preserve cochlear function.

In vivo temporal resolution of acute promyelocytic leukemia progression reveals a role of Klf4 in suppressing early leukemic transformation.

Genome organization plays a pivotal role in transcription, but how transcription factors (TFs) rewire the structure of the genome to initiate and maintain the programs that lead to oncogenic transformation remains poorly understood. Acute promyelocytic leukemia (APL) is a fatal subtype of leukemia driven by a chromosomal translocation between the promyelocytic leukemia (PML) and retinoic acid receptor α (RARα) genes. We used primary hematopoietic stem and progenitor cells (HSPCs) and leukemic blasts that express the fusion protein PML-RARα as a paradigm to temporally dissect the dynamic changes in the epigenome, transcriptome, and genome architecture induced during oncogenic transformation. We found that PML-RARα initiates a continuum of topologic alterations, including switches from A to B compartments, transcriptional repression, loss of active histone marks, and gain of repressive histone marks. Our multiomics-integrated analysis identifies Klf4 as an early down-regulated gene in PML-RARα-driven leukemogenesis. Furthermore, we characterized the dynamic alterations in the Klf4 cis-regulatory network during APL progression and demonstrated that ectopic Klf4 overexpression can suppress self-renewal and reverse the differentiation block induced by PML-RARα. Our study provides a comprehensive in vivo temporal dissection of the epigenomic and topological reprogramming induced by an oncogenic TF and illustrates how topological architecture can be used to identify new drivers of malignant transformation.

Suppressing the activation of protein kinase A as a DNA damage-independent mechanistic lead for dihydromethysticin prophylaxis of NNK-induced lung carcinogenesis.

Our earlier work demonstrated varying potency of dihydromethysticin (DHM) as the active kava phytochemical for prophylaxis of tobacco carcinogen nicotine-derived nitrosamine ketone (NNK)-induced mouse lung carcinogenesis. Efficacy was dependent on timing of DHM gavage ahead of NNK insult. In addition to DNA adducts in the lung tissues mitigated by DHM in a time-dependent manner, our in vivo data strongly implicated the existence of DNA damage-independent mechanism(s) in NNK-induced lung carcinogenesis targeted by DHM to fully exert its anti-initiation efficacy. In the present work, RNA seq transcriptomic profiling of NNK-exposed (2 h) lung tissues with/without a DHM (8 h) pretreatment revealed a snap shot of canonical acute phase tissue damage and stress response signaling pathways as well as an activation of protein kinase A (PKA) pathway induced by NNK and the restraining effects of DHM. The activation of the PKA pathway by NNK active metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) at a concentration incapable of promoting DNA adduct was confirmed in a lung cancer cell culture model, potentially through NNAL binding to and activation of the β-adrenergic receptor. Our in vitro and in vivo data overall support the hypothesis that DHM suppresses PKA activation as a key DNA damage-independent mechanistic lead, contributing to its effective prophylaxis of NNK-induced lung carcinogenesis. Systems biology approaches with a detailed temporal dissection of timing of DHM intake versus NNK exposure are warranted to fill the knowledge gaps concerning the DNA damage-driven mechanisms and DNA damage-independent mechanisms to optimize the implementation strategy for DHM to achieve maximal lung cancer chemoprevention.

Network traffic analysis through node behaviour classification: a graph-based approach with temporal dissection and data-level preprocessing

Network traffic analysis is an important cybersecurity task, which helps to classify anomalous, potentially dangerous connections. In many cases, it is critical not only to detect individual malicious connections, but to detect which node in a network has generated malicious traffic so that appropriate actions can be taken to reduce the threat and increase the system’s cybersecurity. Instead of analysing connections only, node behavioural analysis can be performed by exploiting the graph information encoded in a connection network. Network traffic, however, is temporal data and extracting graph information without a fixed time scope may only unveil macro-dynamics that are less related to cybersecurity threats. To address these issues, a threefold approach is proposed here: firstly, temporal dissection for extracting graph-based information is applied. As the resulting graphs are typically affected by class imbalance (i.e. malicious nodes are under-represented), two novel graph data-level preprocessing techniques - R-hybrid and SM-hybrid - are introduced, which focus on exploiting the most relevant graph substructures. Finally, a Neural Network (NN) and two Graph Convolutional Network (GCN) approaches are compared when performing node behaviour classification. Furthermore, we compare the node classification performance of these supervised models with traditional unsupervised anomaly detection techniques. Results show that temporal dissection parameters affected classification performance, while the data-level preprocessing strategies reduced class imbalance and led to improved supervised node behaviour classification, outperforming anomaly detection models. In particular, Neural Network (NN) outperformed Graph Convolutional Network (GCN) approaches for two attack families and was less affected by class imbalance, yet one GCN performed best overall. The presented study successfully applies a temporal graph-based approach for malicious actor detection in network traffic data.

Temporal dissection of Rai1 function reveals brain-derived neurotrophic factor as a potential therapeutic target for Smith-Magenis syndrome.

Haploinsufficiency of retinoic acid-induced 1 (RAI1) is responsible for Smith-Magenis syndrome (SMS), a childhood neurodevelopmental disorder associated with hyperphagia, obesity and autistic features. We previously showed that constitutive inactivation of one or both copies of Rai1 in the germline or developing brain induces SMS-like neurobehavioral deficits and obesity in mice. By contrast, the postnatal function of Rai1 is unclear. Here, we globally deleted one or both copies of Rai1 during two postnatal developmental windows by generating an inducible Rai1 knockout mouse model. We found that delayed Rai1 deletion at 3 or 8weeks of age had no effect on neurobehavioral functions but resulted in adult-onset obesity and decreased expression of brain-derived neurotrophic factor (Bdnf) in the hypothalamus. Remarkably, genetic overexpression of human Bdnf in Rai1 heterozygous mice reversed SMS-like obesity, hyperphagia, metabolic syndrome-like features and hyposociability. Increasing Bdnf signaling in the paraventricular nucleus of the hypothalamus or the ventromedial nucleus of the hypothalamus was sufficient to mediate the anti-obesity effect. Our work identifies the function of Rai1 in different temporal windows after birth and provides in vivo evidence that increasing Bdnf signaling is therapeutically effective in a preclinical mouse model of SMS.

Paradoxical Temporal Enlargement: An Expansion of Superficial Temporal Fat Pad Following Interfacial Technique for Pterional Craniotomy.

Contour irregularities in the temporal region have been reported previously after procedures involving temporal dissection. In this study, we report paradoxical temporal enlargement (PTE) following interfascial pterional craniotomy. A retrospective review of patients who underwent a unilateral transcranial procedure with frontotemporal approach at our institution between September 2013 and December 2017 was performed. Patients with a previous craniotomy or bilateral craniotomy were excluded. Radiological imaging series including computed tomography and magnetic resonance imaging were utilized to calculate temporal soft tissue volumes both preoperatively and postoperatively by using advanced software technology. Relative soft tissue volume differences between the operative side and the contralateral side were calculated at different time-points including preoperative, 3-months follow-up (3M), 12-months (12M) follow-up, and the last follow-up (LFU, over 1-year). Forty-three patients were included. Mean age was 52.7 ± 4.5 years. Mean follow-up was 27.9 ± 15.8 months. Significant changes of temporal fat pad relative-volume difference were observed between the preoperative and the corresponding 3M (t [82] = -2.8865, P = 0.0050); 12M (t [77] = -4.4321, P < 0.0001), and LFU (t [74] = -4.9862, P < 0.0001) postoperative time points. No significant change of the temporalis muscle was observed between the preoperative and the corresponding 3M (P = 0.3629), 12M (P = 0.1553), or LFU (P = 0.0715). Soft tissue volume showed a significant increase on the operative side between the preoperative and the corresponding LFU (t [74] = -2.5866, P = 0.0117). Paradoxical temporal enlargement with more than 10% volumetric change was observed in 24% of the patients at their LFU (>1-year). This change was not due to temporalis muscle changes. Paradoxical temporal enlargement was due to hypertrophy of the superficial temporal fat pad. Before surgical correction of postoperative temporal contour changes, it is important to obtain imaging and characterize the etiology of the deformity.

MUCOEPIDERMOID CARCINOMA MASKED BY ADJACENT BENIGN NEURAL LESION: A CASE REPORT

<h3>Introduction</h3> Mucoepidermoid carcinomas demonstrate a heterogeneous clinical presentation, occasionally mimicking other lesions (such as mucocele in the oral cavity). We present an unusual case arising in the parotid gland, masked by a neuroma. <h3>Clinical Presentation</h3> A 25-year-old female patient presented to neurology with left facial muscle twitching of 7 years duration, following chemotherapy for Hodgkin lymphoma. Clinical examination revealed muscle fasciculations under the left eye, nose, and angle of mouth. Cranial nerve examination and vision tests were otherwise normal. Magnetic resonance imaging revealed a lesion affecting the extracranial portion of the left facial nerve, with an adjacent parotid gland abnormality, determined as Schwannoma. The patient returned at age 28 with worsening facial weakness, and new magnetic resonance imaging revealed extension of the lesion through the stylomastoid foramen. Following further deterioration of facial muscle function, the lesion was resected with a facial nerve graft. <h3>Histopathology</h3> Sections revealed a well-circumscribed nodule of neural tissue demonstrating direct intraneural infiltration by islands of a cystic epithelial tumor lined by bland cuboidal/columnar epithelium with occasional clear, mucous and intermediate cell types. ABPAS staining confirmed the presence of mucin. The features were of a neuroma infiltrated by mucoepidermoid carcinoma. <h3>Outcome</h3> Following multidisciplinary tumor board discussion, the patient will undergo temporal bone resection, radical parotidectomy, and selective neck dissection. Further outcome will be presented. <h3>Conclusions</h3> Mucoepidermoid carcinomas are the most common salivary malignancies. Our case report highlights that these tumors can show a wide variety of presentation depending on site and size. In this case an adjacent pathology, albeit benign, confused the clinical picture.

The assessment of virtual reality training in antromastoidectomy simulation

Virtual reality (VR) may be a good alternative for cadaveric temporal bone surgical dissection courses, which are an important part of otolaryngology resident’s training. The aim of the study was to assess the VR temporal bone surgery simulator in an antromastoidectomy simulation. The VR system was based on the Geomagic Touch Haptic Device from 3D System. The research was designed as a prospective study, with three sessions of VR simulation training. The group of four ENT specialists unexperienced in otosurgery and 11 otorhinolaryngology residents performed a series of virtual dissections of a VR temporal bone model. Two experts with a broad experience in ear surgery participated in the study as supervisors for all the participants. At the end of each session, the experts controlled the accuracy of the simulated surgery performance assigning positive points for each correctly performed step and negative points for each mistake. After each session, participants of the study were asked to fill in the questionnaire concerning their impression of a VR system simulation. The evaluation of every simulation (total score) was based on the duration of a VR session, the quality of performance (positive points) and the number of mistakes (negative points). During consecutive VR sessions, evident shortening of the length of performance, as well as an improvement in the quality of performance and reduction in mistakes, was observed. Sixty percent of study participants answered that signaling damage to the critical elements was good (40%—sufficient), and 67% assessed that they had made a progress in consecutive sessions. After three sessions, 100% of participants indicated higher self-confidence in relation to their own surgical skills. Also, all the participants indicated that VR training should be included in a routine educational program for medical students. VR training provides a structured, safe and supportive environment to familiarize oneself with complex anatomy and practical skills.

Image-guided Temporal Bone Dissection Course.

Introduction Temporal bone anatomy is complex and demands a profound anatomical knowledge. Association between surgery and imaging helps in the process of learning three-dimensional (3D) anatomy and surgical techniques. High definition temporal bone imaging can play an important role in dissection training. Objective To describe a computed tomography (CT) image-guided temporal bone dissection course for surgical training in otolaryngology and to verify the satisfaction level of the students with the course. Methods Descriptive research. The course took place at a research laboratory, with three experienced temporal bone surgeons. The participants were 12 otolaryngology residents. The laboratory has 7 modern workstations with microscope and monitors linked with a computerized video system. Cadaveric temporal bones were donated to the university. Imaging acquisition of the cadaveric temporal bones used in the course was performed in a multislice CT scanner. The CT images of cadaveric temporal bones were available with real-time access on the laboratory monitor's screens during dissections. Results A total of 13 temporal bones were included for dissection. Students had the opportunity to view on the same screen, simultaneously, both the dissection video and the respective CT images of their temporal bone anatomical specimens. This allowed correlating surgical and imaging aspects of temporal bone anatomy. At the end of the course, participants answered a satisfaction survey. Conclusion Considering imaging methods are routinely used during most otologic surgeries, detailed knowledge of CT imaging should be explored in conjunction with the temporal bone anatomical dissection.

Temporal dissection of an enhancer cluster reveals distinct temporal and functional contributions of individual elements

Many genes are regulated by multiple enhancers that often simultaneously activate their target gene. However, how individual enhancers collaborate to activate transcription is not well understood. Here, we dissect the functions and interdependencies of five enhancer elements that together activate Fgf5 expression during exit from naive murine pluripotency. Four intergenic elements form a super-enhancer, and most of the elements contribute to Fgf5 induction at distinct time points. A fifth, poised enhancer located in the first intron contributes to Fgf5 expression at every time point by amplifying overall Fgf5 expression levels. Despite low individual enhancer activity, together these elements strongly induce Fgf5 expression in a super-additive fashion that involves strong accumulation of RNA polymerase II at the intronic enhancer. Finally, we observe a strong anti-correlation between RNA polymerase II levels at enhancers and their distance to the closest promoter, and we identify candidate elements with properties similar to the intronic enhancer.

Temporal Leptin to Determine Cardiovascular and Metabolic Fate throughout the Life.

Leptin links peripheral adiposity and the central nervous system (CNS) to regulate cardiometabolic physiology. Within the CNS, leptin receptor-expressing cells are a counterpart to circulating leptin, and leptin receptor-mediated neural networks modulate the output of neuroendocrine and sympathetic nervous activity to balance cardiometabolic homeostasis. Therefore, disrupted CNS leptin signaling is directly implicated in the development of metabolic diseases, such as hypertension, obesity, and type 2 diabetes. Independently, maternal leptin also plays a central role in the development and growth of the infant during gestation. Accumulating evidence points to the dynamic maternal leptin environment as a predictor of cardiometabolic fate in their offspring as it is directly associated with infant metabolic parameters at birth. In postnatal life, the degree of serum leptin is representative of the level of body adiposity/weight, a driving factor for cardiometabolic alterations, and therefore, the levels of blood leptin through the CNS mechanism, in a large part, are a strong determinant for future cardiometabolic fate. The current review focuses on highlighting and discussing recent updates for temporal dissection of leptin-associated programing of future cardiometabolic fate throughout the entire life.

The Novel Coronavirus Enigma: Phylogeny and Analyses of Coevolving Mutations Among the SARS-CoV-2 Viruses Circulating in India.

BackgroundThe RNA genome of the emerging novel coronavirus is rapidly mutating, and its human-to-human transmission rate is increasing. Hence, temporal dissection of their evolutionary dynamics, the nature of variations among different strains, and understanding the single nucleotide polymorphisms in the endemic settings are crucial. Delineating the heterogeneous genomic constellations of this novel virus will help us understand its complex behavior in a particular geographical region.ObjectiveThis is a comprehensive analysis of 95 Indian SARS-CoV-2 genome sequences available from the Global Initiative on Sharing All Influenza Data (GISAID) repository during the first 6 months of 2020 (January through June). Evolutionary dynamics, gene-specific phylogeny, and the emergence of the novel coevolving mutations in 9 structural and nonstructural genes among circulating SARS-CoV-2 strains across 12 different Indian states were analyzed.MethodsA total of 95 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID database. Molecular Evolutionary Genetics Analysis, version X software was used to construct the 9 phylogenetic dendrograms based on nucleotide sequences of the SARS-CoV-2 genes. Analyses of the coevolving mutations were done in comparison to the prototype SARS-CoV-2 from Wuhan, China. The secondary structure of the RNA-dependent RNA polymerase/nonstructural protein NSP12 was predicted with respect to the novel A97V mutation.ResultsPhylogenetic analyses revealed the evolution of “genome-type clusters” and adaptive selection of “L”-type SARS-CoV-2 strains with genetic closeness to the bat severe acute respiratory syndrome–like coronaviruses. These strains were distant to pangolin or Middle East respiratory syndrome–related coronavirus strains. With regard to the novel coevolving mutations, 2 groups have been seen circulating in India at present, the “major group” (66/95, 69.4%) and the “minor group” (21/95, 22.1%) , harboring 4 and 5 coexisting mutations, respectively. The “major group” mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6 gene), were unique to the Indian isolates.ConclusionsThis study highlights the rapidly evolving SARS-CoV-2 virus and the cocirculation of multiple clades and subclades. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, interpreting changes in viral pathogenesis, and designing vaccines or other therapeutics.