Outlining the Hidden Curriculum: Perspectives on Successfully Navigating Scientific Conferences.

Scientific conferences and meetings are valuable opportunities for researchers to network, communicate, and develop knowledge. For early career scientists, conferences can also be intimidating, confusing, and overwhelming, especially without having adequate preparation or experience. In this Perspective, we provide advice based on previous experiences navigating scientific meetings and conferences. These guidelines outline parts of the hidden curriculum around preparing for and attending meetings, navigating conference sessions, networking with other scientists, and participating in social activities while upholding a recommended code of conduct.

Domestic dogs in indigenous Amazonian communities: Key players in Leptospira cycling and transmission?

BACKGROUND: Leptospirosis is the world's most common zoonotic disease. Mitigation and control rely on pathogen identification and understanding the roles of potential reservoirs in cycling and transmission. Underreporting and misdiagnosis obscure the magnitude of the problem and confound efforts to understand key epidemiological components. Difficulties in culturing hamper the use of serological diagnostics and delay the development of DNA detection methods. As a result, especially in complex ecosystems, we know very little about the importance of different mammalian host species in cycling and transmission to humans. METHODOLOGY/PRINCIPAL FINDINGS: We sampled dogs from five indigenous Kichwa communities living in the Yasuní National Park in the Ecuadorian Amazon basin. Blood and urine samples from domestic dogs were collected to assess the exposure of these animals to Leptospira and to identify the circulating species. Microscopic Agglutination Tests with a panel of 22 different serovars showed anti-leptospira antibodies in 36 sampled dogs (75%), and 7 serogroups were detected. Two DNA-based detection assays revealed pathogenic Leptospira DNA in 18 of 19 dog urine samples (94.7%). Amplicon sequencing and phylogenetic analysis of 16S rRNA and SecY genes from 15 urine samples revealed genetic diversity within two of three different Leptospira species: noguchii (n = 7), santarosai (n = 7), and interrogans (n = 1). CONCLUSIONS/SIGNIFICANCE: The high prevalence of antibodies and Leptospira DNA provides strong evidence for high rates of past and current infections. Such high prevalence has not been previously reported for dogs. These dogs live in the peridomestic environment in close contact with humans, yet they are free-ranging animals that interact with wildlife. This complex web of interactions may explain the diverse types of pathogenic Leptospira observed in this study. Our results suggest that domestic dogs are likely to play an important role in the cycling and transmission of Leptospira. Future studies in areas with complex ecoepidemiology will enable better parsing of the significance of genotypic, environmental, and host characteristics.

Successful management of pulmonary edema secondary to accidental electrocution in a young dog.

BACKGROUND: Human records describe pulmonary edema as a life-threatening complication of electric shock. Successful management requires prompt recognition and intensive care. However, in companion animals, electrocutions are rarely reported, even though domestic environments are full of electrical devices and there is always the possibility of accidental injury. Therefore, it is important for veterinarians to know more about this condition in order to achieve successful patient outcomes. CASE PRESENTATION: A 3-month-old male Labrador Retriever was presented with a history of transient loss of consciousness after chewing on a household electrical cord. On admission, the puppy showed an orthopneic position with moderate respiratory distress. Supplemental oxygen via nasal catheter was provided, but the patient showed marked worsening of respiratory status. Point-of-care ultrasound exams suggested neurogenic pulmonary edema due to electrical shock close to the central nervous system and increased B-lines without evidence of cardiac abnormalities. Mechanical ventilation of the patient was initiated using volume-controlled mode with a tidal volume of 9 to 15 ml/kg until reaching an end-tidal carbon dioxide ≤ 40 mm Hg, followed by a stepwise lung-recruitment maneuver in pressure-controlled mode with increases of the peak inspiratory pressure (15 to 20 cm H2O) and positive end-expiratory pressure (3 to 10 cm H2O) for 30 min, and return to volume-controlled mode with a tidal volume of 15 ml/kg until reaching a peripheral oxygen saturation ≥ 96%. Weaning from the ventilator was achieved in six hours, and the patient was discharged two days after admission without neurological or respiratory deficits. CONCLUSIONS: We present a rather unusual case of a neurogenic pulmonary edema subsequent to accidental electrocution in a dog. Timely diagnosis by ultrasound and mechanical ventilation settings are described. Our case highlights that pulmonary edema should be considered a potentially life-threatening complication of electrical shock in small animal emergency and critical care medicine.

Development has the answer: Unraveling psychiatric disorders via thalamocortical organoids.

Dissecting the role of the thalamus in neuropsychiatric disorders requires new models to analyze complex genetic interactions. In this issue of Cell Stem Cell, Shin et al. use patient-derived thalamocortical organoids to investigate 22q11.2 microdeletion impact on thalamic development, revealing significant transcriptional dysregulation linked to psychiatric disorders.

A Genetic Tool to Identify Predators Responsible for Livestock Attacks in South America and Recommendations for Human-Wildlife Conflict Mitigation.

Livestock predation induces global human-wildlife conflict, triggering the retaliatory killing of large carnivores. Although domestic dogs (Canis familiaris) contribute to livestock depredation, blame primarily falls on wild predators. Dogs can also transmit pathogens between wildlife, domestic animals, and humans. Therefore, the presence of free-ranging dogs can have negative consequences for biodiversity conservation, smallholder economy, food supply, and public health, four of the United Nations' Sustainable Developed Goals (SDGs) for 2030. In Ecuador, where livestock sustains rural households, retaliatory poaching threatens Andean bear (Tremarctos ornatus), jaguar (Panthera onca), and puma (Puma concolor) populations. However, the role of dogs in these incidents remains underexplored. The present study evaluates the possibility of reliable molecular identification of predatory species from DNA traces in bite wounds. Our results revealed the presence of dog saliva on four out of six livestock carcasses presumably attacked by wild predators. These findings highlight the importance of rectifying misinformation about large carnivores in Ecuador and the need to control dog populations. We recommend that local administrations incorporate DNA analysis into livestock predation events to examine how common the problem is, and to use the analysis to develop conflict mitigation strategies which are essential for the conservation of large carnivores.

SARS-CoV-2 infection in brown-headed spider monkeys (Ateles fusciceps) at a wildlife rescue center on the coast of Ecuador-South America.

Human populations can be affected in unpredictable ways by the emergence and spread of zoonotic diseases. The COVID-19 (coronavirus disease of 2019) pandemic was a reminder of how devastating these events can be if left unchecked. However, once they have spread globally, the impact of these diseases when entering non-exposed wildlife populations is unknown. The current study reports the infection of brown-headed spider monkeys (Ateles fusciceps) at a wildlife rescue center in Ecuador. Four monkeys were hospitalized, and all tested positive for SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) by RT-qPCR (Quantitative Reverse Transcription PCR). Fecal samples (n = 12) from monkeys at the rescue center also tested positive; three zookeepers responsible for feeding and deworming the monkeys also tested positive, suggesting human-animal transmission. Whole genome sequencing identified most samples' omicron clade 22B BA.5 lineage. These findings highlight the threat posed by an emerging zoonotic disease in wildlife species and the importance of preventing spillover and spillback events during epidemic or pandemic events.IMPORTANCEAlthough COVID-19 (coronavirus disease of 2019) has been primarily contained in humans through widespread vaccination, the impact and incidence of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus) and its transmission and epidemiology in wildlife may need to be addressed. In some natural environments, the proximity of animals to humans is difficult to control, creating perfect scenarios where susceptible wildlife can acquire the virus from humans. In these places, it is essential to understand how transmission can occur and to develop protocols to prevent infection. This study reports the infection of brown-headed spider monkeys with SARS-CoV-2, a red-listed monkey species, at a wildlife recovery center in Ecuador. This study reports the infection of brown-headed spider monkeys with SARS-CoV-2, indicating the potential for transmission between humans and wildlife primates and the importance of preventing such events in the future.

Unpacking the Drivers of LGBT+ Legislation.

This paper stems from the hypothesis that there are various key factors rooted in economic, political, and social grounds which actively influence and determine the adoption and evolution of LGBT+ rights in the legal framework of any country. The goal of this research is to analyze these factors and understand how they channel the LGBT+ legislation in our present world. Assuming there is an asymmetry in this application and by extension in LGBT+ individuals' human rights, which are often ignored if not deprived in many parts of the world, this study seeks to understand the reasons behind that asymmetry. Based on a sample of 127 countries, a correlation analysis and a Panel data model were developed to analyze the real impact of these factors.

Lung Cancer Screening in Head and Neck Cancer Patients: An Untapped Opportunity.

BACKGROUND: Despite evidence demonstrating that lung cancer screening (LCS) decreases mortality, widespread implementation is lagging. Efforts to identify and recruit patients for LCS are in need. Candidacy for LCS is based on identifiable risk factors, many of which overlap with those of head and neck malignancies. Thus, we aimed to evaluate the prevalence of candidacy for LCS in the head and neck cancer patient population. METHODS: We performed a review of anonymous surveys collected from patients who presented to a head and neck cancer clinic. Variables collected from these surveys included age, biologic sex, smoking history, and head and neck cancer history. Patients' candidacy for screening was determined, and descriptive analyses were performed. RESULTS: A total of 321 patient surveys were reviewed. Mean age was 63.7 years, and 195 (60.7%) were men. In this sample, 19 (5.91%) were current smokers, and 112 (34.9%) were former smokers, having quit an average of 19.4 years prior to completing the survey. Average pack-years was 29.3. Of the 321 patients surveyed, 60 (18.7%) would qualify for LCS using current guidelines. However, among those 60 patients who qualified for LCS, only 15 (25%) patients had been offered screening and only 14 (23.3%) had been screened. CONCLUSIONS: We have importantly demonstrated both a substantial prevalence of candidacy for LCS in the head and neck cancer population as well as disappointingly low levels of screening utilization in this group of patients. We have identified this setting as a key patient population that ought to be targeted for information about and access to LCS.

Seroconversion in Galapagos Sea Lions (Zalophus wollebaeki) Confirms the Presence of Canine Distemper Virus in Rookeries of San Cristóbal Island.

BACKGROUND: The emblematic Galapagos sea lion (GSL-Zalophus wollebaeki) has faced an important population decline over the last four decades. There are multiple environmental and biological factors that might be implied in this decrease. Recently, evidence of various zoonotic infectious diseases that can be potential threats has been reported. Considering that in some islands of the archipelago the risk of transmission of infectious diseases may be promoted by the increasing population of domestic dogs, epidemiological vigilance and search of new pathogens are essential. The canine distemper virus (CDV), one of the viral pathogens that generate the most concern for the agencies responsible for the management and conservation of the Galapagos pinnipeds, was detected in the GSL in 2010. However, there is scarce information about its impact on GSL health and about its epidemiology. METHODS: In this study, 110 GSL serum samples were collected during the summer of 2016 and 2017. All samples were exposed to VERO dog SLAM cells expressing the canine SLAM receptor. RESULTS: Our results showed a significative increase (p = 0.04) in the frequency of neutralizing antibodies to CDV in the 2017 (53.1%) samples compared to the 2016 samples (19.6%). CONCLUSIONS: Our work confirmed the continuous and increasing circulation of the CDV in the GSL and highlights the importance of monitoring emerging diseases that can be transmitted from domestic to wildlife species. Vigilance of CDV is essential to understand the role of this virus in GSL mortality and to take informed decisions for wildlife conservation.

Light and shadow of watch-and-wait strategy in rectal cancer: oncological result, clinical outcomes, and cost-effectiveness analysis.

BACKGROUND: The watch-and-wait (WW) strategy is a potential option for patients with rectal cancer who obtain a complete clinic response after neoadjuvant therapy. The aim of this study is to analyze the long-term oncological outcomes and perform a cost-effectiveness analysis in patients undergoing this strategy for rectal cancer. MATERIAL AND METHODS: The data of patients treated with the WW strategy were prospectively collected from January 2015 to January 2020. A control group was created, matched 1:1 from a pool of 480 patients undergoing total mesorectal excision. An independent company carried out the financial analysis. Clinical and oncological outcomes were analyzed in both groups. Outcome parameters included surgical and follow-up costs, quality-adjusted life years (QALYs), and the incremental cost per QALY gained or the incremental cost-effectiveness ratio (ICER). RESULTS: Forty patients were included in the WW group, with 40 patients in the surgical group. During a median follow-up period of 36 months, metastasis-free survival (MFS) and overall survival (OS) were similar in the two groups. In the WW group, nine (22%) local regrowths were detected in the first 2 years. The permanent stoma rate was slightly higher after salvage surgery in the WW group compared to the surgical group (48.5% vs 20%, p < 0.01). The cost-effectiveness analysis was slightly better for the WW group, especially for low rectal cancer compared to medium-high rectal cancer (ICER = - 108,642.1 vs ICER = - 42,423). CONCLUSIONS: The WW strategy in locally advanced rectal cancer offers similar oncological outcomes with respect to the surgical group and excellent results in quality of life and cost outcomes, especially for low rectal cancer. Nonetheless, the complex surgical field during salvage surgery can lead to a high permanent stoma rate; therefore, the careful selection of patients is mandatory.

Acute cardiac tamponade during atrial flutter ablation: improved hemodynamics after positive pressure ventilation: a case report.

INTRODUCTION: Acute cardiac tamponade is a rare event during any type of interventional or surgical procedure. It can occur during electrophysiology procedures due to radiofrequency ablation, lead or catheter manipulation, transseptal puncture, laser lead extractions, or left atrial appendage occlusion device positioning. Cardiac tamponade is difficult to study in a prospective manner, and case reports and case series are important contributions to understanding the best options for patient care. An 87-year-old Caucasian male patient breathing spontaneously developed acute tamponade during an atrial flutter ablation. Pericardial drain insertion was difficult, and hypotension failed to respond to epinephrine boluses. The patient became hypoxemic and hypercarbic, requiring intubation. Unexpectedly, the blood pressure markedly increased postintubation and remained in a normal range until the pericardium was drained. CONCLUSION: Spontaneous ventilation is considered important to maintain venous return to the right heart during cardiac tamponade. However, spontaneous ventilation reduces venous return to the left heart and worsens the paradoxical pulse in tamponade. Intravenous vasopressors are thought to be ineffective during cardiac tamponade. Our patient maintained pulmonary blood flow as indicated by end-tidal carbon dioxide measurements but had no measurable systemic blood pressure during spontaneous ventilation. Our case demonstrates that tracheal intubation and positive pressure ventilation can transiently improve left heart venous return, systemic perfusion, and drug delivery to the systemic circulation.

Leptospirosis in horses: Sentinels for a neglected zoonosis? A systematic review.

Background and Aim: Leptospirosis is considered a neglected tropical zoonosis in low-income countries due to surveillance system limitations and non-specificity of symptoms. Humans become infected through direct contact with carrier animals or indirectly through Leptospira-contaminated environments. Conventionally, equines have been considered an uncommon source of leptospirosis, but recent publications in Latin America suggest that their role in the maintenance and dispersion of the bacteria could be more relevant than expected, as horses are susceptible to a wide variety of zoonotic Leptospira spp. from domestic and wild animals with which they share the environment. A systematic review of the published literature was conducted to compile the available information on Leptospira spp. in Ecuador, with a special focus on equine leptospirosis, to better understand the epidemiology of the bacterium and identify possible knowledge gaps. Materials and Methods: A systematic review of the published literature was conducted in PubMed, SciELO and Web of Science databases to compile the available information on Leptospira spp. in Ecuador, with a special focus on equine leptospirosis, to better understand the epidemiology of the bacterium. We used a combination of the terms (Leptospira OR Leptospirosis) AND Ecuador, without restrictions on language or publication date. Results: Our literature review reveals that published scientific information is very scarce. Eighteen full-text original scientific articles related to Leptospira or leptospirosis cases in Ecuador were included in the systematic review. Most of the studies reported data obtained from one of the four regions (Coast), and specifically from only one of the 24 Provinces of Ecuador (Manabí), which evidence a large information bias at the geographical level. Furthermore, only the studies focused on humans included clinical signs of leptospirosis and there is only one study that analyzes the presence of Leptospira spp. in water or soil as a risk factor for pathogen transmission. Finally, only one study investigated Leptospira in horses. Conclusion: Since sentinel species can provide useful data on infectious diseases when epidemiologic al information is lacking, and horses could be considered excellent sentinel species to reveal circulating serovars, we propose developing a nationwide surveillance system using horses. This cost-effective epidemiological survey method provides a baseline for implementing specific prevention and control programs in Ecuador and neighboring developing countries.

Domestic dogs in indigenous Amazonian communities: key players in Leptospira cycling and transmission?

Background: Leptospirosis is the world's most common zoonotic disease. Mitigation and control rely on pathogen identification and understanding the roles of potential reservoirs in cycling and transmission. Underreporting and misdiagnosis obscure the magnitude of the problem and confound efforts to understand key epidemiological components. Difficulties in culturing hamper the use of serological diagnostics and delay the development of DNA detection methods. As a result, especially in complex ecosystems, we know very little about the importance of different mammalian host species in cycling and transmission to humans. Methodology/Principal Findings: We sampled five indigenous Kichwa communities living in the Yasuní National Park in the Ecuadorian Amazon basin. Blood and urine samples from domestic dogs were collected to assess the exposure of these animals to Leptospira, and to identify the circulating species. Microscopic Agglutination Tests with a panel of 22 different serovars showed anti-leptospira antibodies in 36 sampled dogs (75%), and 10 serotypes were detected. Two DNA-based detection assays revealed pathogenic Leptospira DNA in 18 of 19 dog urine samples (94.7%). Amplicon sequencing and phylogenetic analysis of 16s rDNA and SecY genes from 15 urine samples revealed genetic diversity within two of three different Leptospira species: noguchii (n=7), santarosai (n=7), and interrogans (n=1). Conclusions/Significance: The high prevalence of antibodies and Leptospira DNA provides strong evidence for high rates of past and current infections. Such high prevalence has not been previously reported for dogs. These dogs live in the peridomestic environment in close contact with humans, yet they are free-ranging animals that interact with wildlife. This complex web of interactions may explain the diverse types of pathogenic Leptospira observed in this study. Our results suggest that domestic dogs are likely to play an important role in the cycling and transmission of Leptospira. Future studies in areas with complex ecoepidemiology will enable better parsing of the significance of genotypic, environmental, and host characteristics.

Nanostructured Porous Silicon for Bone Tissue Engineering: Kinetics of Particle Degradation and Si-Controlled Release.

Nanostructured porous silicon (pSi) is a synthetic silicon-based material. Its biocompatibility and bioresorbability in body fluids make pSi an appealing biomaterial for tissue engineering, with surfaces characteristics facilitating human cell adhesion and differentiation. The resorption kinetics of such porous biomaterials is crucial for in vivo bone regeneration, in order to adapt biomaterial resorption to tissue formation, and to control the release of loaded bioactive molecules. We investigated pSi as a bioactive scaffold for bone tissue engineering, with an emphasis on kinetics of pSi resorption and silicon release. PSi particles and chips were fabricated from crystalline silicon, and functionalized by oxidation and chemical grafting of amine groups to mimic biological structures. Materials resorption over time was investigated with Raman spectroscopy, infrared spectroscopy, and Scanning Electron Microscopy. Silicon release was followed by mass spectrometry. Particle degradation and inclusion in newly formed bone were studied in vivo. The in vitro experiments revealed that non-oxidized pSi had an accelerated initial dissolution in ddH2O and an inhibition of initial Si release in SBF. This high reactivity also led to transformation towards amorphous non-resorbable silica when incubated in SBF. PSi resorption started immediately with a maximal dissolution in the first 24 h. Later, the dissolution rate decreased over time. In comparison, the resorption process of oxidized pSi seemed delayed, but more continuous. This delayed dissolution increased the bioactivity and stability, leading to enhanced bone formation in vivo. Delayed pSi degradation provided a constant surge of silicic acid over time and promoted bone regeneration, demonstrating the high potential of pSi for bone tissue engineering: Oxidized pSi were almost completely resorbed after 2 months of healing, with remaining partially dissolved particles surrounded by newly formed bone. On the contrary, non-oxidized particles were still obviously present after 2 months with limited bone regeneration. This delayed resorption is consistent with the in vitro observations in SBF, and particles' transformation towards silica.

Can 3D imaging modeling recognize functional tissue and predict liver failure? A retrospective study based on 3D modelling of the major hepatectomies after hepatic modulation.

BACKGROUND: Thanks to the introduction of radiomics, 3d reconstruction can be able to analyse tissues and recognise true hypertrophy from non-functioning tissue in patients treated with major hepatectomies with hepatic modulation.The aim of this study is to evaluate the performance of 3D Imaging Modelling in predict liver failure. METHODS: Patients submitted to major hepatectomies after hepatic modulation at Sanchinarro University Hospital from May 2015 to October 2019 were analysed. Three-dimensional reconstruction was realised before and after surgical treatment. The volumetry of Future Liver Remnant was calculated, distinguishing in Functional Future Liver Remnant (FRFx) i.e. true hypertrophy tissue and Anatomic Future Liver Remnant (FRL) i.e. hypertrophy plus no functional tissue (oedema/congestion) These volumes were analysed in patients with and without post hepatic liver failure. RESULTS: Twenty-four procedures were realised (11 ALPPS and 13 PVE followed by major hepatectomy). Post hepatic liver failure grade B and C occurred in 6 patients. The ROC curve showed a better AUC for FRFxV (74%) with respect to FRLV (54%) in prediction PHLF > B. The increase of anatomical FRL (iFRL) was superior in the ALPPS group (120%) with respect to the PVE group (73%) (p = 0,041), while the increase of functional FRFX (iFRFx) was 35% in the ALLPS group and 46% in the PVE group (p > 0,05), showing no difference in the two groups. CONCLUSION: The 3D reconstruction model can allow optimal surgical planning, and through the use of specific algorithms, can contribute to differential functioning liver parenchyma of the FLR.

Pronation Reveals a Heterogeneous Response of Global and Regional Respiratory Mechanics in Patients With Acute Hypoxemic Respiratory Failure.

OBJECTIVES: Experimental models suggest that prone position and positive end-expiratory pressure (PEEP) homogenize ventral-dorsal ventilation distribution and regional respiratory compliance. However, this response still needs confirmation on humans. Therefore, this study aimed to assess the changes in global and regional respiratory mechanics in supine and prone positions over a range of PEEP levels in acute respiratory distress syndrome (ARDS) patients. DESIGN: A prospective cohort study. PATIENTS: Twenty-two intubated patients with ARDS caused by COVID-19 pneumonia. INTERVENTIONS: Electrical impedance tomography and esophageal manometry were applied during PEEP titrations from 20 cm H2O to 6 cm H2O in supine and prone positions. MEASUREMENTS: Global respiratory system compliance (Crs), chest wall compliance, regional lung compliance, ventilation distribution in supine and prone positions. MAIN RESULTS: Compared with supine position, the maximum level of Crs changed after prone position in 59% of ARDS patients (n = 13), of which the Crs decreased in 32% (n = 7) and increased in 27% (n = 6). To reach maximum Crs after pronation, PEEP was changed in 45% of the patients by at least 4 cm H2O. After pronation, the ventilation and compliance of the dorsal region did not consistently change in the entire sample of patients, increasing specifically in a subgroup of patients who showed a positive change in Crs when transitioning from supine to prone position. These combined changes in ventilation and compliance suggest dorsal recruitment postpronation. In addition, the subgroup with increased Crs postpronation demonstrated the most pronounced difference between dorsal and ventral ventilation distribution from supine to prone position (p = 0.01), indicating heterogeneous ventilation distribution in prone position. CONCLUSIONS: Prone position modifies global respiratory compliance in most patients with ARDS. Only a subgroup of patients with a positive change in Crs postpronation presented a consistent improvement in dorsal ventilation and compliance. These data suggest that the response to pronation on global and regional mechanics can vary among ARDS patients, with some patients presenting more dorsal lung recruitment than others.

Expression and function of Caenorhabditis elegans UNCP-18, a paralog of the SM protein UNC-18.

Sec1/Munc18 (SM) proteins are important regulators of SNARE complex assembly during exocytosis throughout all major animal tissue types. However, expression of a founding member of the SM family, UNC-18, is mostly restricted to the nervous system of the nematode Caenorhabditis elegans, where it is important for synaptic transmission. Moreover, unc-18 null mutants do not display the lethality phenotype associated with (a) loss of all Drosophila and mouse orthologs of unc-18 and (b) with complete elimination of synaptic transmission in C. elegans. We investigated whether a previously uncharacterized unc-18 paralog, which we named uncp-18, may be able to explain the restricted expression and limited phenotypes of unc-18 null mutants. A reporter allele shows ubiquitous expression of uncp-18. Analysis of uncp-18 null mutants, unc-18 and uncp-18 double null mutants, as well as overexpression of uncp-18 in an unc-18 null mutant background, shows that these 2 genes can functionally compensate for one another and are redundantly required for embryonic viability. Our results indicate that the synaptic transmission defects of unc-18 null mutants cannot necessarily be interpreted as constituting a null phenotype for SM protein function at the synapse.

CUT homeobox genes: transcriptional regulation of neuronal specification and beyond.

CUT homeobox genes represent a captivating gene class fulfilling critical functions in the development and maintenance of multiple cell types across a wide range of organisms. They belong to the larger group of homeobox genes, which encode transcription factors responsible for regulating gene expression patterns during development. CUT homeobox genes exhibit two distinct and conserved DNA binding domains, a homeodomain accompanied by one or more CUT domains. Numerous studies have shown the involvement of CUT homeobox genes in diverse developmental processes such as body axis formation, organogenesis, tissue patterning and neuronal specification. They govern these processes by exerting control over gene expression through their transcriptional regulatory activities, which they accomplish by a combination of classic and unconventional interactions with the DNA. Intriguingly, apart from their roles as transcriptional regulators, they also serve as accessory factors in DNA repair pathways through protein-protein interactions. They are highly conserved across species, highlighting their fundamental importance in developmental biology. Remarkably, evolutionary analysis has revealed that CUT homeobox genes have experienced an extraordinary degree of rearrangements and diversification compared to other classes of homeobox genes, including the emergence of a novel gene family in vertebrates. Investigating the functions and regulatory networks of CUT homeobox genes provides significant understanding into the molecular mechanisms underlying embryonic development and tissue homeostasis. Furthermore, aberrant expression or mutations in CUT homeobox genes have been associated with various human diseases, highlighting their relevance beyond developmental processes. This review will overview the well known roles of CUT homeobox genes in nervous system development, as well as their functions in other tissues across phylogeny.

Two-Photon Light Trigger siRNA Transfection of Cancer Cells Using Non-Toxic Porous Silicon Nanoparticles.

The concept of using two-photon excitation in the NIR for the spatiotemporal control of biological processes holds great promise. However, its use for the delivery of nucleic acids has been very scarcely described and the reported procedures are not optimal as they often involve potentially toxic materials and irradiation conditions. This work prepares a simple system made of biocompatible porous silicon nanoparticles (pSiNP) for the safe siRNA photocontrolled delivery and gene silencing in cells upon two-photon excitation. PSiNP are linked to an azobenzene moiety, which possesses a lysine group (pSiNP@ICPES-azo@Lys) to efficiently complex siRNA. Non-linear excitation of the two-photon absorber system (pSiNP) followed by intermolecular energy transfer (FRET) to trans azobenzene moiety, result in the photoisomerization of the azobenzene from trans to cis and in the destabilization of the azobenzene-siRNA complex, thus inducing the delivery of the cargo siRNA to the cytoplasm of cells. Efficient silencing in MCF-7 expressing stable firefly luciferase with siRNAluc against luciferase is observed. Furthermore, siRNA against inhibitory apoptotic protein (IAP) leads to over 70% of MCF-7 cancer cell death. The developed technique using two-photon light allows a unique high spatiotemporally controlled and safe siRNA delivery in cells in few seconds of irradiation.

Thoracic Aortic Aneurysm Presenting as a Subacute Cough.

The suprasternal aortic notch cardiac point of care ultrasound (POCUS) window is a useful view for evaluating thoracic aortic pathologies. However, it is not routinely included in the standard cardiac POCUS exam despite its ability to capture emergent pathologies such as aortic dissection and thoracic aortic aneurysm (TAA). Ruptured aortic aneurysms can present with sudden, severe chest or back pain, as well as hemodynamic instability, resulting in a high mortality. We present an atypical case of a patient with hemoptysis who was found to have a contained aortic rupture. In this case, POCUS, specifically the suprasternal aortic notch view, was used to expedite definitive care.