PET imaging of brain aromatase in humans and rhesus monkeys by 11C-labeled cetrozole analogs

Aromatase is an estrogen synthetic enzyme that plays important roles in brain functions. To quantify aromatase expression in the brain by positron emission tomography (PET), we had previously developed [11C]cetrozole, which showed high specificity and affinity. To develop more efficient PET tracer(s) for aromatase imaging, we synthesized three analogs of cetrozole. We synthesized meta-cetrozole, nitro-cetrozole, and iso-cetrozole, and prepared the corresponding 11C-labeled tracers. The inhibitory activities of these three analogs toward aromatase were evaluated using marmoset placenta, and PET imaging of brain aromatase was performed using the 11C-labeled tracers in monkeys. The most promising analog in the monkey study, iso-cetrozole, was evaluated in the human PET study. The highest to lowest inhibitory activity of the analogs toward aromatase in the microsomal fraction from marmoset placenta was in the following order: iso-cetrozole, nitro-cetrozole, cetrozole, and meta-cetrozole. This order showed good agreement with the order of the binding potential (BP) of each 11C-labeled analog to aromatase in the rhesus monkey brain. A human PET study using [11C]iso-analog showed a similar distribution pattern of binding as that of [11C]cetrozole. The time–activity curves showed that elimination of [11C]iso-cetrozole from brain tissue was faster than that of 11C-cetrozole, indicating more rapid metabolism of [11C]iso-cetrozole. [11C]Cetrozole has preferable metabolic stability for brain aromatase imaging in humans, although [11C]iso-cetrozole might also be useful to measure aromatase level in living human brain because of its high binding potential.

Herpes zoster following mRNA-1273 COVID-19 vaccination

Sir, Skin rashes have been associated with COVID-19 and studies suggest the inclusion of skin diseases in the list of COVID-19 symptoms. Skin eruptions are also associated with the mRNA-1273 COVID-19 vaccine. Findings by Baden et al. [1] describe immediate injection-site reactions observed in 84.2% of participants after the first dose, with delayed onset reactions—on or after day eight—occurring much more infrequently, 0.8% after the first dose and 0.2% after the second dose. Blumenthal et al. [2] discuss twelve cases of delayed vaccine reactions, with all patients experiencing reactions in the vaccination site. Herein, we describe two cases of herpes zoster within days of receiving their first mRNA-1273 vaccine. Both cases presented to the same dermatology clinic. A 77-year-old male presented with a bumpy, itchy, red rash on the upper right arm and axilla three days following an mRNA-1273 vaccine injection. The symptoms continued to worsen and the patient was clinically diagnosed with herpes zoster and treated with valacyclovir (Fig. 1). Another patient, also a 77-year-old male, complained of a rash located on the right upper arm and axilla. It was a red, itchy, bumpy rash that the patient developed two days after an mRNA-1273 vaccine injection (Fig. 2). Both rashes demonstrated a similar distribution pattern and both patients responded well to valacyclovir with the resolution of the erythema; however, one patient did have residual post-herpetic neuralgia.

Dual-energy CT in gout patients: Do all colour-coded lesions actually represent monosodium urate crystals?

Background Dual-energy CT (DECT) can acknowledge differences in tissue compositions and can colour-code tissues with specific features including monosodium urate (MSU) crystals. However, when evaluating gout patients, DECT frequently colour-codes material not truly representing MSU crystals and this might lead to misinterpretations. The characteristics of and variations in properties of colour-coded DECT lesions in gout patients have not yet been systematically investigated. The objective of this study was to evaluate the properties and locations of colour-coded DECT lesions in gout patients. Methods DECT of the hands, knees and feet were performed in patients with suspected gout using factory default gout settings, and colour-coded DECT lesions were registered. For each lesion, properties [mean density (mean of Hounsfield Units (HU) at 80 kV and Sn150kV), mean DECT ratio and size] and location were determined. Subgroup analysis was performed post hoc evaluating differences in locations of lesions when divided into definite MSU depositions and possibly other lesions. Results In total, 4033 lesions were registered in 27 patients (23 gout patients, 3918 lesions; 4 non-gout patients, 115 lesions). In gout patients, lesions had a median density of 160.6 HU and median size of 6 voxels, and DECT ratios showed an approximated normal distribution (mean 1.06, SD 0.10), but with a right heavy tail consistent with the presence of smaller amounts of high effective atomic number lesions (e.g. calcium-containing lesions). The most common locations of lesions were 1st metatarsophalangeal (MTP1), knee and midtarsal joints along with quadriceps and patella tendons. Subgroup analyses showed that definite MSU depositions (large volume, low DECT ratio, high density) had a similar distribution pattern, whereas possible calcium-containing material (high DECT ratio) and non-gout MSU-imitating lesions (properties as definite MSU depositions in non-gout patients) were primarily found in some larger joints (knee, midtarsal and talocrural) and tendons (Achilles and quadriceps). MTP1 joints and patella tendons showed only definite MSU depositions. Conclusion Colour-coded DECT lesions in gout patients showed heterogeneity in properties and distribution. MTP1 joints and patella tendons exclusively showed definite MSU depositions. Hence, a sole focus on these regions in the evaluation of gout patients may improve the specificity of DECT scans.

Tardigrades from Iztaccíhuatl Volcano (Trans-Mexican Volcanic Belt), with the Description of Minibiotus citlalium sp. nov. (Eutardigrada: Macrobiotidae)

The study of tardigrade diversity in Mexico is at early stage of development, to date, 56 extant species have been reported. To identify the tardigrade fauna associated with mosses in the Iztaccíhuatl volcano, we performed a systematic sampling along an altitudinal and multi-habitat gradient. A total of 57 moss samples were collected, 233 adults, 20 exuviae, and 40 free-laid tardigrade eggs were extracted from them. Five species were identified, and three putative species were determined. Diphascon mitrense and Minibiotus sidereus represents new records for Mexico and North America, while Adropion scoticum is a new record for Mexico. Additionally, one new species, Minibiotus citlalium sp. nov. was discovered; it resembles to Min. constellatus, Min. sidereus and Min. pentannulatus by the presence of a similar distribution pattern of star-shaped pores in the dorsal cuticle arranged in 11 transverse rows, which become double in the segments of the legs I–III, and by a very large star-shaped pore (5–6 tips) on each leg of the fourth pair. Minibiotus citlalium sp. nov. differs from other Minibiotus species mainly by macroplacoid length sequence, presence of both small and large star-shaped pores on the external surface on all legs, and by egg processes with inconspicuous ornamentation.

Glomerular Deposition of Nephritis-Associated Plasmin Receptor (NAPlr) and Related Plasmin Activity: Key Diagnostic Biomarkers of Bacterial Infection-related Glomerulonephritis

It is widely known that glomerulonephritis (GN) often develops after the curing of an infection, a typical example of which is GN in children following streptococcal infections (poststreptococcal acute glomerulonephritis; PSAGN). On the other hand, the term “infection-related glomerulonephritis (IRGN)” has recently been proposed, because infections are usually ongoing at the time of GN onset in adult patients, particularly in older patients with comorbidities. However, there has been no specific diagnostic biomarker for IRGN, and diagnosis is based on the collection of several clinical and pathological findings and the exclusion of differential diagnoses. Nephritis-associated plasmin receptor (NAPlr) was originally isolated from the cytoplasmic fraction of group A streptococcus as a candidate nephritogenic protein for PSAGN and was found to be the same molecule as streptococcal glyceraldehyde-3-phosphate dehydrogenase and plasmin receptor. NAPlr deposition and related plasmin activity were observed with a similar distribution pattern in the glomeruli of patients with PSAGN. However, glomerular NAPlr deposition and plasmin activity could be observed not only in patients with PSAGN but also in patients with other glomerular diseases, in whom a preceding streptococcal infection was suggested. Furthermore, such glomerular staining patterns have been demonstrated in patients with IRGN induced by bacteria other than streptococci. This review discusses the recent advances in our understanding of the pathogenesis of bacterial IRGN, which is characterized by NAPlr and plasmin as key biomarkers.

Population frequencies of vkorc1 c1173t polymorphism, which determining the organism sensitivity to warfarin, in forest nenets and nganasans of northern siberia

Полиморфизм C1173T гена VKORC1 является одним из ключевых факторов, определяющих как этнические, так и индивидуальные различия в чувствительности к антикоагулянту варфарину и его поддерживающей дозе у пациентов при лечении тромбозозависимых заболеваний. В связи с этим, на популяционном уровне проведено исследование полиморфизма VKORC1 C1173T среди коренных представителей лесных ненцев Ямало-Ненецкого автономного округа и нганасан полуострова Таймыр Красноярского края. Генотипирование однонуклеотидных замен в гене VKORC1 проводилось в режиме реального времени с использованием конкурирующих TaqMan-зондов. Выявлено, что вариант VKORC1 1173T встречается с высокой частотой в изученных популяциях: 67% у лесных ненцев и 94% у нганасан. Этот показатель существенно и статистически значимо выше, чем у европейцев, и имеет схожий характер распространения с таковым у азиатов Китая и Японии. Результаты нашего исследования расширяют знания о полиморфизме гена VKORC1 в человеческих популяциях, а также способствуют развитию персонализированной медицины по отношению к коренным жителям Сибири, так как генетический статус человека, имеющего вариант 1173T, может учитываться в целях достижения максимально безопасной и эффективной терапии варфарином при тромбозозависимых заболеваниях. Polymorphism C1173T of the VKORC1 gene is one of the key factors determining both ethnic and individual differences in the sensitivity to the anticoagulant warfarin and its maintenance dose in patients in the treatment of thrombosis-dependent diseases. In this regard, at the population level the VKORC1 C1173T polymorphism was studied in indigenous populations of the Forest Nenets (the Yamal-Nenets Autonomous Okrug) and Nganasans (the Taimyr Peninsula of the Krasnoyarsk region). Genotyping of C1173T single nucleotide substitution in the VKORC1 gene was carried out in real time using competing TaqMan probes. It was revealed that the variant VKORC1 1173T occurs with a high frequency in the studied populations: 67% in Forest Nenets and 94% in Nganasans. This indicator is significantly higher than that of Europeans, and has a similar distribution pattern with that of Asians. The results of our study expand knowledge about VKORC1 gene polymorphism in human populations, and also promote the development of personalized medicine in relation to indigenous people of Siberia, since the genetic status of a person with variant 1173T can be taken into account at an individual level in order to achieve the most safe and effective warfarin therapy of thrombosis-dependent diseases.

Evaluation of the Abundance of DNA-Binding Transcription Factors in Prokaryotes

The ability of bacteria and archaea to modulate metabolic process, defensive response, and pathogenic capabilities depend on their repertoire of genes and capacity to regulate the expression of them. Transcription factors (TFs) have fundamental roles in controlling these processes. TFs are proteins dedicated to favor and/or impede the activity of the RNA polymerase. In prokaryotes these proteins have been grouped into families that can be found in most of the different taxonomic divisions. In this work, the association between the expansion patterns of 111 protein regulatory families was systematically evaluated in 1351 non-redundant prokaryotic genomes. This analysis provides insights into the functional and evolutionary constraints imposed on different classes of regulatory factors in bacterial and archaeal organisms. Based on their distribution, we found a relationship between the contents of some TF families and genome size. For example, nine TF families that represent 43.7% of the complete collection of TFs are closely associated with genome size; i.e., in large genomes, members of these families are also abundant, but when a genome is small, such TF family sizes are decreased. In contrast, almost 102 families (56.3% of the collection) do not exhibit or show only a low correlation with the genome size, suggesting that a large proportion of duplication or gene loss events occur independently of the genome size and that various yet-unexplored questions about the evolution of these TF families remain. In addition, we identified a group of families that have a similar distribution pattern across Bacteria and Archaea, suggesting common functional and probable coevolution processes, and a group of families universally distributed among all the genomes. Finally, a specific association between the TF families and their additional domains was identified, suggesting that the families sense specific signals or make specific protein-protein contacts to achieve the regulatory roles.

Xenochlora meridionalis sp. nov. (Hymenoptera: Apidae), a new halictine bee from eastern Brazil as evidence of past connections between Amazonia and Atlantic Forest

We describe a new species of the bee genus Xenochlora Engel, Brooks & Yanega, 1997, X. meridionalis sp. nov., based on a single female collected in the coastal forests of southeastern Brazil, in the state of Espírito Santo. The disjunct distribution exhibited by Xenochlora, with species in northern South America and in the Atlantic Forest of eastern Brazil, is discussed in light of current knowledge about other taxa with similar distribution pattern.

Comparación de los productos de TSM L3 generados a partir de los sensores AVHRR y MODIS frente al Golfo San Jorge, Argentina

<p>Since the early 1980s, the AVHRR sensor on board the NOAA satellites has provided SST estimates to the scientific community in general. Towards the end of the 1990s, a new generation of radiometers was added, combining a wider range of spectral measurements with improvements in technology, such as the MODIS sensor on board the Terra and Aqua satellites. The development of this last sensor was based on the years of NOAA/AVHRR series. Understanding the relationship between products derived from different sensors is critical to the continuous long-term monitoring of any variable and the construction of continuous time series. The objective of this work was to make a comparison of the monthly SST values for the 2003-2006 period calculated from data from the NOAA/ AVHRR series versus Aqua-MODIS on a sector of the middle Argentina Continental shelf off the San Jorge Gulf. For both sensors, the isotherms show a similar distribution pattern in all months. Pearson’s correlation coefficient was high, both in the seasonal (&gt; 0.9) and monthly (&gt; 0.8) analyzes. The comparative analysis of the temperature estimated by both sensors shows that SST products are similar and can be used to analyze large and continuous time series.</p>

Neural Differentiation in HDAC1-Depleted Cells Is Accompanied by Coilin Downregulation and the Accumulation of Cajal Bodies in Nucleoli

Cajal bodies (CBs) are important compartments containing accumulated proteins that preferentially regulate RNA-related nuclear events, including splicing. Here, we studied the nuclear distribution pattern of CBs in neurogenesis. In adult brains, coilin was present at a high density, but CB formation was absent in the nuclei of the choroid plexus of the lateral ventricles. Cells of the adult hippocampus were characterized by a crescent-like morphology of coilin protein. We additionally observed a 70 kDa splice variant of coilin in adult mouse brains, which was different to embryonic brains and mouse pluripotent embryonic stem cells (mESCs), characterized by the 80 kDa standard variant of coilin. Here, we also showed that depletion of coilin is induced during neural differentiation and HDAC1 deficiency in mESCs caused coilin accumulation inside the fibrillarin-positive region of the nucleoli. A similar distribution pattern was observed in adult brain hippocampi, characterized by lower levels of both coilin and HDAC1. In summary, we observed that neural differentiation and HDAC1 deficiency lead to coilin depletion and coilin accumulation in body-like structures inside the nucleoli.