Ca and Nε-lysine acetylation regulate the CALR-ATG9A interaction in the lumen of the endoplasmic reticulum.

The acetylation of autophagy protein 9 A (ATG9A) in the lumen of the endoplasmic reticulum (ER) by ATase1 and ATase2 regulates the induction of reticulophagy. Analysis of the ER-specific ATG9A interactome identified calreticulin (CALR), an ER luminal Ca-binding chaperone, as key for ATG9A activity. Specifically, if acetylated, ATG9A is sequestered by CALR and prevented from engaging FAM134B and SEC62.

A new chitinozoan assemblage from the Middle Devonian Los Monos Formation (sub-Andean basin, southern Bolivia) and its biozonal implications for Western Gondwana.

Chitinozoans recovered from one section of the Middle Devonian Los Monos Formation in the TCB X-1001-Tacobo borehole, sub-Andean basin of Bolivia, have been analysed. Eleven from the eighteen processed cutting samples yielded specimens that allowed taxonomic study. Eleven genera and thirty-five chitinozoan species were identified from the Los Monos Formation with four of them recorded for the first time in Western Gondwana.

Graduate certificate on risk analysis for the Agrifood sector at the University of Buenos Aires.

Argentina has an extensive experience in the biosafety assessment of transgenic crops. The regulatory framework celebrated 30 years of existence in 2021 and has pioneered the establishment of the biosafety systems in Latin America. During this period, Argentina's regulatory framework evolved to keep up with the advancements in plant and animal biotechnology and in risk assessment criteria, as new knowledge and experience was being gained.

Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model.

Neurofibromatosis Type 1 (NF1) is one of the most common genetically inherited disorders that affects 1 in 3000 children annually. Clinical manifestations vary widely but nearly always include the development of cutaneous, plexiform and diffuse neurofibromas that are managed over many years. Recent single-cell transcriptomics profiling efforts of neurofibromas have begun to reveal cell signaling processes.

An out of the box treatment for an infected pseudoaneurysm: Deep to superficial femoral artery transposition.

An infected pseudoaneurysm is a condition that has become more common in recent years, with the proliferation of endovascular intervention and the use of intravenous drugs. If left untreated, an infected pseudoaneurysm can progress to rupture, which can lead to life-threatening hemorrhage. No clear consensus has been reached among vascular surgeons regarding the management of infected pseudoaneurysms, and the literature describes a wide range of treatment techniques.

Feasibility of Intravascular Lithotripsy for the Treatment of Calcified Supra-Aortic Vessels: A Case Report and Literature Review.

Purpose: To report a case of coronary-subclavian steal syndrome (CSSS) due to a history of a left internal mammary artery (LIMA) to left anterior descending (LAD) artery coronary bypass (CABG) and a heavily calcified ostial left subclavian artery (LSA) occlusion, that was treated with intravascular lithotripsy (IVL) technique and to summarize the current trends of IVL treatment for supra-aortic vessels.

Case Report: A 64-year-old woman with progressive intermittent angina pectoris and a history of LIMA to LAD bypass underwent coronary angiography which demonstrated complete ostial occlusion of the LSA. Via brachial access, the patient underwent Shockwave IVL balloon treatment of the LSA and stent-graft implantation.

The circadian clock is disrupted in pancreatic cancer.

Disruption of the circadian clock is linked to cancer development and progression. Establishing this connection has proven beneficial for understanding cancer pathogenesis, determining prognosis, and uncovering novel therapeutic targets. However, barriers to characterizing the circadian clock in human pancreas and human pancreatic cancer-one of the deadliest malignancies-have hindered an appreciation of its role in this cancer.

Common femoral adventitial cystic disease in a young female patient.

Adventitial cystic disease (ACD) is a rare condition that typically presents in young healthy men with symptoms of claudication. ACD is characterized by formation of a mucinous cyst within the adventitia of a blood vessel, usually in the popliteal artery, causing compression of the vessel's lumen and leading to reduced flow and symptoms of claudication. We have presented a rare case of ACD of the common femoral artery in a young female patient that was treated successfully with resection and femoral vein graft interposition reconstruction.

A novel endovascular treatment for transcatheter aortic valve embolization.

In the present report, we have described the case of an 82-year-old obese man who had required transcatheter aortic valve replacement to treat severe symptomatic aortic stenosis. During implantation, the balloon-mounted valve became dislodged and embolized to the ascending aorta. A second valve was successfully implanted after several failed attempts to reposition the first one into the aortic annulus.

A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling.

Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), produced by cyclic GMP-AMP synthase (cGAS), stimulates the production of type I interferons (IFN). Here we show that cGAMP activates DNA damage response (DDR) signaling independently of its canonical IFN pathways. Loss of cGAS dampens DDR signaling induced by genotoxic insults.

Assessment of Mosaicism and Detection of Cryptic Alleles in CRISPR/Cas9-Engineered Neurofibromatosis Type 1 and Mutant Porcine Models Reveals Overlooked Challenges in Precision Modeling of Human Diseases.

Genome editing in pigs has been made efficient, practical, and economically viable by the CRISPR/Cas9 platform, representing a promising new era in translational modeling of human disease for research and preclinical development of therapies and devices. Porcine embryo microinjection provides a universally available, efficient option over somatic-cell nuclear transfer, but requires that critical considerations be made in genotypic validation of the models that routinely go unaddressed. Accurate validation of genotypes is especially important when modeling genetic disorders, such as neurofibromatosis type 1 (NF1) that exhibits complex genotype-phenotypic relationships.

17β-Estradiol and estrogen receptor α protect right ventricular function in pulmonary hypertension via BMPR2 and apelin.

Women with pulmonary arterial hypertension (PAH) exhibit better right ventricular (RV) function and survival than men; however, the underlying mechanisms are unknown. We hypothesized that 17β-estradiol (E2), through estrogen receptor α (ER-α), attenuates PAH-induced RV failure (RVF) by upregulating the procontractile and prosurvival peptide apelin via a BMPR2-dependent mechanism. We found that ER-α and apelin expression were decreased in RV homogenates from patients with RVF and from rats with maladaptive (but not adaptive) RV remodeling.

Generation of an Allelic Series at the Ahr Locus Using an Edited Recombinant Approach.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and a member of the PER-ARNT-SIM (PAS) superfamily of environmental sensors. The AHR is involved in a series of biological processes including adaptive metabolism of xenobiotics, toxicity of certain environmental pollutants, vascular development, fertility, and immune function. Mouse models, including the Ahr null and Ahr conditional null (Ahrfx) mice, are widely used for the study of AHR-mediated biology and toxicity.

Pmp22 super-enhancer deletion causes tomacula formation and conduction block in peripheral nerves.

Copy number variation of the peripheral nerve myelin gene Peripheral Myelin Protein 22 (PMP22) causes multiple forms of inherited peripheral neuropathy. The duplication of a 1.4 Mb segment surrounding this gene in chromosome 17p12 (c17p12) causes the most common form of Charcot-Marie-Tooth disease type 1A, whereas the reciprocal deletion of this gene causes a separate neuropathy termed hereditary neuropathy with liability to pressure palsies (HNPP).

Familiarity in the Context of Risk Assessment of Transgenic Crops: Focus on Some Countries in the Americas.

Problem formulation is the formal opening stage of a risk assessment that determines its purpose and scope and hence guides the gathering of information data. The concepts of familiarity and history of safe use are an integral part of problem formulation. These concepts do not replace the case-by-case approach and are not taken as safety standards but are valuable components of the process that shape the generation of plausible, testable risk hypotheses.

Sex-specific deficits in neurite density and white matter integrity are associated with targeted disruption of exon 2 of the Disc1 gene in the rat.

Diffusion tensor imaging (DTI) has provided remarkable insight into our understanding of white matter microstructure and brain connectivity across a broad spectrum of psychiatric disease. While DTI and other diffusion weighted magnetic resonance imaging (MRI) methods have clarified the axonal contribution to the disconnectivity seen in numerous psychiatric diseases, absent from these studies are quantitative indices of neurite density and orientation that are especially important features in regions of high synaptic density that would capture the synaptic contribution to the psychiatric disease state. Here we report the application of neurite orientation dispersion and density imaging (NODDI), an emerging microstructure imaging technique, to a novel Disc1 svΔ2 rat model of psychiatric illness and demonstrate the complementary and more specific indices of tissue microstructure found in NODDI than those reported by DTI.

Capacities for the Risk Assessment of GMOs: Challenges to Build Sustainable Systems.

The need for functional risk assessment bodies in general, and in the biosafety field in particular, demands continued efforts and commitment from regulatory agencies, if results that are sustainable in time are to be achieved. The lack of formal processes that ensure continuity in the application of state of the art scientific criteria, the high rotation in some cases or the lack of experienced professionals, in others, is a challenge to be addressed. Capacity building initiatives with different approaches and degrees of success have been implemented in many countries over the years, supported by diverse governmental and non-governmental organizations.

Cardiac tamponade and coronary artery pseudoaneurysm after brachial arterial embolectomy, possible role for an aberrant origin of the right coronary artery.

A patient developed hemopericardium shortly after left brachial arterial embolectomy using an embolectomy catheter. Evaluation disclosed evolving pseudoaneurysm of the right coronary artery that was successfully managed by stenting. Misplacement of the embolectomy catheter within the coronary vessel was facilitated by an anomalous origin of the right coronary artery.

Complete B Cell Deficiency Reduces Allograft Inflammation and Intragraft Macrophages in a Rat Kidney Transplant Model.

Background: Increasingly, it is being appreciated that B cells have broad roles beyond the humoral response and are able to contribute to and regulate inflammation. The specific role of B cells in the pathogenesis of early allograft inflammation remains unclear.

Methods: To address this question, we generated B cell-deficient (B) Lewis rats via clustered regularly interspaced short palindromic repeats (CRISPR) technology.

Acute mesenteric ischemia: guidelines of the World Society of Emergency Surgery.

Acute mesenteric ischemia (AMI) is typically defined as a group of diseases characterized by an interruption of the blood supply to varying portions of the small intestine, leading to ischemia and secondary inflammatory changes. If untreated, this process will eventuate in life threatening intestinal necrosis. The incidence is low, estimated at 0.

Phase Ib Safety, Two-Dose Study of MultiGeneAngio in Patients with Chronic Critical Limb Ischemia.

Critical limb ischemia (CLI) is the most severe presentation of peripheral arterial disease. We developed cell-based therapy entailing intra-arterial injection of autologous venous endothelial cells (ECs) modified to express angiopoietin 1, combined with autologous venous smooth muscle cells (SMCs) modified to express vascular endothelial growth factor. This combination promoted arteriogenesis in animal models and was safe in patients with limiting claudication.

Mouse mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies.

While the aging process is central to the pathogenesis of age-dependent diseases, it is poorly understood at the molecular level. We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases, suggesting that the responsible gene regulates retinal aging, and its impairment results in age-dependent disease. We determined that a mutation in the transmembrane 135 () is responsible for these phenotypes.

Cathepsin Activity-Based Probes and Inhibitor for Preclinical Atherosclerosis Imaging and Macrophage Depletion.

Background And Purpose: Cardiovascular disease is the leading cause of death worldwide, mainly due to an increasing prevalence of atherosclerosis characterized by inflammatory plaques. Plaques with high levels of macrophage infiltration are considered "vulnerable" while those that do not have significant inflammation are considered stable; cathepsin protease activity is highly elevated in macrophages of vulnerable plaques and contributes to plaque instability. Establishing novel tools for non-invasive molecular imaging of macrophages in plaques could aid in preclinical studies and evaluation of therapeutics.

Development of a construct-based risk assessment framework for genetic engineered crops.

Experience gained in the risk assessment (RA) of genetically engineered (GE) crops since their first experimental introductions in the early nineties, has increased the level of familiarity with these breeding methodologies and has motivated several agencies and expert groups worldwide to revisit the scientific criteria underlying the RA process. Along these lines, the need to engage in a scientific discussion for the case of GE crops transformed with similar constructs was recently identified in Argentina. In response to this need, the Argentine branch of the International Life Sciences Institute (ILSI Argentina) convened a tripartite working group to discuss a science-based evaluation approach for transformation events developed with genetic constructs which are identical or similar to those used in previously evaluated or approved GE crops.

Acute Type B Aortic Pathology Mimicking Acute Type A Intramural Hematoma with Organ Malperfusion.

The management of acute Stanford Type A intramural hematoma (IMH) of the aorta remains controversial. Most surgeons advocate emergency surgery in a manner similar to frank acute Type A dissection. Others recommend a conservative approach to this distinct clinicopathological entity.