Hirudiniasis, or leech infestation, is a rare parasitic condition typically involving external skin or mucosal surfaces. We report a case of scrotal hirudiniasis, an 11 cm long leech discovered within the scrotal sac of a 15-year-old male. He initially developed hematuria due to periurethral leech attachment, which resolved following catheterization and bladder irrigation. A week later, he presented with acute scrotal pain and swelling. Ultrasound revealed a tubular, mobile structure near the left vas deferens. Surgical exploration identified an 11 cm leech within the tunica vaginalis, without any external entry wound or urethra-cutaneous fistula. Two plausible routes of entry are suggested: retrograde movement via the vas deferens or migration through perineal fascial planes following urethral breach. This case underscores the need to consider unusual parasitic causes in patients presenting with acute scrotum in endemic regions.
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SMART (stroke-like migraine attacks after radiation therapy) syndrome is a rare neurological disorder characterized by stroke-like symptoms and migraine-like headaches years after brain radiotherapy. Its pathophysiology remains unclear but is linked to vascular damage, inflammation, and mitochondrial dysfunction. This study presents two cases, emphasizing clinical and radiological findings. MRI is crucial for diagnosis, often showing transient cortical hyperintensities and contrast enhancement. Misdiagnosis as stroke or tumor recurrence may lead to unnecessary interventions. Increasing awareness is essential for accurate diagnosis and management. Further research is needed to refine diagnostic criteria and optimize treatment strategies for this rare but significant condition.
Detection and management of suspected intraoperative myocardial ischemia are critical for patient outcome. Following induction of general anesthesia, sudden global T-wave inversion appeared on continuous electrocardiogram (ECG) monitoring, raising suspicion for acute myocardial ischemia and prompting cancellation of surgery. The patient underwent a thorough evaluation for myocardial ischemia despite negative circulating troponin, but all tests were negative. The T-wave inversion persisted for 2 months. This case highlights the need for caution in interpreting isolated perioperative ECG changes in the era of heightened awareness for perioperative myocardial ischemia and routine troponin screening, to avoid unnecessary and potentially invasive investigations.
Over the last three decades, dogma-breaking studies have refuted the brain's assumed immune isolation. Echoing Ramón y Cajal metaphor of neurons as "butterflies," I propose viewing the brain as a neuroimmune garden, with neurons sustained by immune-cell nectar, supporting maintenance, plasticity, protection, and repair.
Organellar genomes are both a resource for reconstructing organismal phylogenies and interesting subjects for evolutionary studies. Herein, we focused on the organellar genomes of eustigmatophytes (eustigs), a class of the algal phylum Ochrophyta with a growing biotechnological potential, and massively expanded the existing limited sample by 51 new organellar genomes. Analyses of this large dataset provided a robustly resolved eustig phylogeny and important insights into the evolution of unique features of eustig organellar genomes. Eustig plastomes are rather stable in terms of the gene content and order, with only minor differences stemming from differential gene loss and rare lineage-specific gain. In contrast, eustig mitogenomes vary broadly in their gene order, the content of "accessory" genes, and substitution rates. Notably, the new data illuminated the origin of some of the organellar genes previously deemed eustig-specific. Thus, the plastid gene ycf95 most likely is an extremely divergent version of ycf35, and the mitochondrial genes orfX and orfY evolved, respectively, by rps4 duplication and extreme divergence of rps1 ortholog. Most interestingly, we identified five previously unrecognized orthogroups of mysterious mitochondrial orfs that are patchily distributed across eustigs yet likely evolved in the ancestor of this class. These orfs have no discernible homologs outside eustigmatophytes but are predicted to encode multipass membrane proteins with a soluble C-terminal domain. Finally, our results revise some of the previous conclusions regarding the mitochondrial translation in eustigs and suggest the recruitment of a group of unusual tRNAs for a translation-independent function in the genus Vischeria.
Cells possess an intrinsic recycling system called macroautophagy/autophagy, which delivers obsolete or damaged cytoplasmic components into the vacuole for degradation and reuse. Autophagy-mediated breakdown of organellar membrane lipids supplies fatty acids for the synthesis of triacylglycerols (TAGs), which are then packaged into subcellular organelles called lipid droplets (LDs). Conversely, autophagy contributes to TAG turnover by delivering LDs into vacuoles for breakdown by resident acid lipases. Additionally, LDs can undergo degradation through cytosolic lipolysis mediated by SDP1 (Sugar-Dependent1) lipase in Arabidopsis. Autophagy-mediated LD, a process referred to as lipophagy, has been described in plants. Nevertheless, the precise mechanisms of lipophagy and the specific types of vacuoles involved remain unclear. Here, we show that overexpression of autophagy genes ATG5 or ATG8 promotes autophagic activity and significantly reduces LD accumulation. We demonstrate that the decreased LD abundance is not due to increased LD degradation mediated by SDP1 but is dependent on autophagy. The abundance of vacuoles specifically labeled by δ-TIP3 (delta-tonoplast intrinsic protein 3) was markedly decreased in ATG5-overexpressing lines. In addition, disruption of autophagic genes prevented the formation of both δ-TIP3-positive vacuoles and the mysterious vacuolar lumen structures previously termed bulbs, indicating their autophagic origin. Furthermore, confocal imaging analysis revealed close associations between LDs and δ-TIP3-labeled vacuoles, as well as the presence of LDs within vacuoles delimited by δ-TIP3. Together, our findings indicate that overexpression of autophagy genes triggers lipophagy and identify a distinct type of vacuole involved in this process.Abbreviation: ATG: autophagy related; AV: autophagic vacuole; ConA: concanamycin A; DsRed: Discosoma sp red fluorescent protein; ER: endoplasmic reticulum; GFP: green fluorescent protein; LD: lipid droplet; OLE: oleosin; SDP1: Sugar-Dependent1; TAG: triacylglycerol; TIP: tonoplast intrinsic protein; TLC: thin-layer chromatography.
Although humans are uniquely prolific tool users, children consistently struggle to innovate tools in experimental paradigms, a finding that challenges perceptions of children as natural creative beings. This paradox may reflect limitations in experimental paradigms that impose rigid structures misaligned with children's natural, exploratory problem-solving tendencies. The present study examined whether more open-ended contexts better reveal children's capacity for tool innovation and explored the processes underlying creative problem solving. A total of 126 British children (66 girls, 60 boys, 0 nonbinary), aged 4-7 years (M = 6.04, SD = 0.94), were tested in dyads on two tool innovation tasks, each presented in either a goal-directed or open-ended condition using a counterbalanced design. The tasks were themed to encourage play. In the pirate-themed hook task, treasure was available to retrieve from a hole on an island by creating a pipe cleaner hook, and in the alien-themed floating-object task, a mysterious object was available to retrieve by filling a tube with water to make the object float. Innovation rates did not differ across the goal-directed and open-ended conditions for either task. However, further analysis revealed that, regardless of condition and age, children who engaged in more exploration were more likely to innovate successful tool solutions. These findings underscore the central role of exploration in children's tool innovation and highlight the importance of examining problem-solving processes beyond outcome-based measures. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
In November 2020, an alert for a "mysterious disease" among fishermen was issued. Fishermen are particularly subjected to dermatoses due to their constant contact with seawater, fish, crustaceans, and fishing equipment that may contain harmful agents. The study aimed to examine the alert, identify the causative agent and suggest preventive and control measures. This was a cross-sectional study of dermatoses in Dakar (Senegal) from October 11 to November 30, 2020, using quantitative and qualitative methods within a 'One Health' approach." The investigation included bacterio-virological, anatomopathological and toxicological examinations. Data were analyzed using Epi info and QGIS (case mapping), We observed all confidentiality measures during the study. A total of 555 cases were diagnosed with an attack rate of 5.4% among fishermen and no deaths were reported. There was a delay in epidemic detection and notification. The epidemic was most prevalent among people from coastal areas. Average age of cases was 22 ± 9 years, and all were male and artisanal fishermen by profession. Patients presented with fever (16%), cutaneous pain (100%) and mucocutaneous lesions (100%) consisting of vesicles, papules and ulcerations localized on exposed areas of the body, external genitalia and oral mucosa, with severe cases (8%). Toxicology revealed the presence of a toxic alga (V. rugosum) in marine equipments. The notion of a sea trip in the 24-48 hours before the onset of the disease was found in 92%. Majority of cases (74%) did not have full personal protective equipment (PPE). The proportion of people without full protection was 83% among those who developed severe forms. People without full protection were more exposed to severe forms than those with full PPE; (OR = 1.818; 95% CI [0.829 - 3.988]). The investigation has linked the epidemic to a probable algal origin. We need to promote the use of personal protective equipment and improve the early warning and notification system.
Temperature-sensitive transient receptor potential melastatin subfamily 4 (TRPM4) ion channels convert intracellular calcium increases into membrane depolarization, thereby linking these two powerful cellular signaling pathways in diverse physiological processes. TRPM4 mutations cause severe human hereditary cardiovascular and skin diseases; mysteriously, while these mutations are gain-of-function in nature, they affect the heart and the skin in a mutually exclusive manner. Here, we show that phosphatidylinositol 4,5-bisphosphate (PIP2) lipid is a required cofactor for TRPM4 activity by tightly regulating its calcium sensitivity. We detected two PIP2 binding sites and located the high-affinity site adjacent to the S4-S5 linker. We demonstrated that skin disease-associated TRPM4 mutations relieve the tight control of PIP2, resulting in elevated channel activity but only at the body surface temperature. In contrast, heart diseases are associated with mutations known to boost the number of channels, an effect we found to be annihilated by channel desensitization outside the body core. Indeed, dendritic cells from transgenic mice carrying a skin disease mutant exhibited elevated migration at 25-to-30°C range compared to those from normal mice, but no difference was observed at 37°C. These findings shed light on a molecular mechanism for dynamic regulation of cellular signaling in physiology and diseases.
To engineer modular polyketide synthases that reliably yield stereocomplex products, a detailed understanding of how their enzymatic domains collectively operate is essential. How their enoylreductase (ER) domains function to install either d-or l-oriented alkyl substituents remains largely mysterious. In this study, we investigated the stereoselectivity of ERs and how they work with other domains within tetraketide-heptaketide synthase platforms constructed from components of the pikromycin and rapamycin synthases. We first determined how ER and acyl carrier protein (ACP) domains associate by mutagenically probing the consensus solution predicted by AlphaFold using an in vitro tetraketide synthase platform. Since ERs were found to contact residues conserved in ACPs from diverse module types, we tested whether ERs operate when inserted into modules that only contain ketoreductase and dehydratase domains in several in vivo platforms. ER-inserted modules were observed to generate both unsaturated and saturated intermediates. Increased production of the saturated intermediate was realized when the downstream KS was also swapped for a KS from an ER-containing module. To access products with desired methyl group orientations, it was necessary to consider how the methyl groups interact with the KS of the module that installed them, as well as with the KS of the downstream module. Additionally, we interconverted d- and l-type ERs by swapping a 14-residue loop and propose the molecular basis for how ERs set stereocenters. This research provides new strategies for controlling the orientations of alkyl substituents in complex polyketides and enables access to stereochemical libraries of polyketide drug leads.
In this article, the complicated history of understanding and defining autism is presented. Descriptions of important contributors and studies that are not widely known or remembered are also included and incorporated into the historical timeline. The first descriptions of probable cases of autism date back to the 18th century, but at that time, the individuals were diagnosed with mental retardation or "silent madness." When the term autism was coined by Eugen Bleuler, it was related to the "inner world" to describe severe cases of schizophrenia. The first explicit description of autism, as we understand it today, was published in 1944 by Leo Kanner, who showed both similarities and differences between autism and childhood schizophrenia. Understanding the core problems related to autism took several decades. Groundbreaking studies conducted by Rutter et al. and Kolvin et al. determined that autism was separate from schizophrenia disorder 36 years after its official introduction (Diagnostic and Statistical Manual of Mental Disorders, Third Edition, in 1980). In 1988, Rutter and Schopler stated that autism had the most validated diagnosis in child psychiatry. However, each subsequent classification introduced major changes and was significantly different from the previous ones. The aim was to optimize the diagnosis and provide optimal care for affected individuals. Our knowledge of autism is broad, and there are still allegations concerning the quality of the currently applicable classifications. Given how many years it has taken and the various approaches that have been used to understand autism, it may indeed be one of the most mysterious disorders in humans. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
The operator wave function provides a fine-grained description of quantum chaos and of the irreversible growth of simple operators into increasingly complex ones. Remarkably, at finite temperature, this wave function can acquire a phase that increases linearly with the operator's size, a phenomenon called size winding. Although size winding occurs naturally in a holographic setting, the emergence of a coherent phase in a scrambled operator remains mysterious from the standpoint of a thermalizing quantum many-body system. In this work, we elucidate this phenomenon by introducing the related concept of Krylov winding, whereby the operator wave function acquires a phase that winds linearly with the Krylov index. We show that Krylov winding is a generic feature of quantum chaotic systems and is a direct consequence of the universal operator growth bound hypothesis. It gives rise to size winding under two additional conditions: (i) a low-rank mapping between the Krylov and size bases, which ensures phase alignment among operators of the same size, and (ii) the saturation of the "chaos-operator growth" bound λ_{L}≤2α (with λ_{L} the Lyapunov exponent and α the growth rate), which ensures a linear phase dependence on size. For systems that do not saturate this bound, with h=λ_{L}/2α<1, the winding with Pauli size ℓ becomes superlinear, behaving as ℓ^{1/h}. We illustrate these results with two classes of microscopic models: the Sachdev-Ye-Kitaev (SYK) model and its variants, and a disordered k-local spin model.
The recently found spin-triplet superconductor candidate UTe2 has attracted enormous attention. Here, we report the finding of superconductivity up to Tc ≈ 4 K in one of its siblings, i.e., UAs2 under pressure. UAs2 shows metallic behavior with an antiferromagnetic transition at about 274 K at ambient pressure. Upon applying pressure, this transition is pushed down to lower temperatures with improved electric conductivity. When the pressure rises beyond about 20 GPa, superconductivity occurs together with the emergence of a linear temperature dependence of normal state resistance in low-temperature region. The superconductivity with the highest onset Tc ≈ 4.05 K is reached under a pressure of 26.8 GPa, and it is robust against magnetic field with the μ0Hc2(0) ~ 12 T, far beyond the Pauli limit. Higher pressures will suppress the superconductivity and bring back the Fermi liquid behavior. Our results open an avenue for investigating the unconventional superconductivity concerning the mysterious 5f-band electrons in uranium (U)-based system.
We discuss here physics and evolution of globular proteins with a focus on the basic units of their structure and function, closed loops and elementary functional loops. A starting point of the journey here is a prebiotic evolution, in which short linear peptides and corresponding RNA duplexes with traits determined by demands to survive and to move on in the harshness of the Origin of Life emerged first. Next, we follow the fate of ring-like peptides, which apparently were the "Dayhoff fragments" that passed through abiogenic transition, formed first functional domains followed by their inclusion in multidomain structures, formation of complexes, assemblies, and molecular machines in later stages. I argue that physics, specifically polymer nature of protein chains, not only served as a determinant of the basic units of proteins-closed loops but also could play a decisive role in determining the size of another important structural unit-domain-based on the polymer nature of nucleic acids that governed the optimal ring closure size of DNA molecules. The protein closed loops served as scaffold for carrying elementary functions-descendants of ancient ring-like peptides, combinations of which provided the modern protein function universe. Another alliance between physics and evolution discussed here is the allosteric regulation of protein function, which is based on the structural dynamics underlying the allosteric signal transduction and its regulatory role. While the physics drive the structure-based conserved patterns of allosteric signalling determined by the folds, the evolution brings in a sequence diversity, allowing to alternate the allosteric communication and to make it archetypal for distinct functional (super)families using the same fold as the structural platform. Considering only few above aspects, I show that important lessons from the hand-in-hand walk of physics and evolution already helped to achieve the current state-of-the-art in understanding of protein structure and function. I conclude, however, that there is still even more to learn from Nature about long and remaining mainly mysterious 3.5 billion years endeavor.
How to recognize death and how to build up memories related to it is both solemn and sacred and full of mystery to the Chinese people, who have a deep traditional culture. This study focuses on the "digital mourning" of American basketball superstar Kobe Bryant by Chinese fans on social media platforms. Employing an exploratory research approach that combines virtual ethnography with semi-structured interviews, it analyzes how digital mourning for celebrities influences Chinese fans' memories of death and mourning rituals. The study found that following Kobe's death, social media accounts served as platforms for fans to engage with the deceased, bringing the emotional release central to the mourning process into the public sphere through "digital mourning" and shifting mourning rituals from the "private" realm of the individual to the "public" realm of the collective. Social media accounts used by Kobe during his lifetime, functioning as virtual extensions of physical mausoleums, have transformed into "digital tombs" where the living collectively commemorate the departed. Within the virtual, digital space constructed around this "digital tombs", fan communities not only spontaneously create "imagined interactions" with the deceased by transcending the barriers of time and space, but also seek emotional release and psychological solace. "Digital mourning" for celebrities places grief within a public sphere open to discussion, reshaping Chinese fans' perceptions of death in the social media era while also serving as a crucial entry point for analyzing the impact of digital mourning on the Chinese public's traditional memories of death.
The prothrombinase complex, comprised of factor (f) Xa and fVa, converts prothrombin to thrombin through sequential cleavage at two sites in a rapid and processive manner. The molecular basis of prothrombin processing is an enzymatical mystery that to solve requires structural insight into how the substrate and intermediate bind to prothrombinase. Here we present two 3.1 Å cryo-EM structures of prothrombinase bound to prothrombin and to meizothrombin. The prothrombin complex revealed a surprising interaction between the end of the heavy chain of fVa with exosite I of prothrombin, accounting for 70% of the contact interface. Triggering of the zymogen-to-protease conformational change following cleavage at Arg320 alters all domain-domain and fVa interactions observed for prothrombin, and results in a large-scale rearrangement of meizothrombin that presents the second cleavage site (Arg271) for processing. Together, these structures reveal a remarkable enzymatic mechanism that requires the active participation of the substrate itself, and introduces a new paradigm of 'substrate allostery'.
The modified nucleotide β-D-glucopyranosyloxymethyluracil (Base J) is found uniquely in kinetoplastids. Accumulating evidence has linked J to gene expression regulation, though its precise mechanistic role has remained elusive. Recent studies suggest J recruits chromatin restructuring and transcription termination complexes to DNA via a novel J-Binding Protein (JBP3), revealing diverse mechanism of J function. This review provides a comprehensive summary of Base J, exploring its biological roles and outlook as a parasite-specific therapeutic target. The necessity of functional J studies in species beyond Trypanosoma brucei will also be addressed, essential to uncover J functional divergence amongst kinetoplastids.