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  • Desai Skytte posted an update 2 weeks ago

    Domains of unknown function protein family 1517 (DUF1517) in Ammopiptanthus mongolicus, could be induced by abiotic stresses, whose upstream regulatory sequence might be an ideal source of abiotic-induced promoter. In this study, a 1026-bp promoter of AmDUF1517 from A. mongolicus was cloned. Selitrectinib mouse Five deletion fragments (Full, Q1-Q4) of different length of the AmDUF1517 promoter were fused with the β-glucuronidase (GUS) reporter and transformed into Arabidopsis thaliana. The deletion analysis showed that sequences Full, Q1 and Q3 responded well to mannitol, NaCl and 4 °C stresses, while Q2 and Q4 segments did not. The Q3 fragment (280 bp; -280 to -1 bp) showed the highest promoter activity under normal and mannitol, NaCl and 4 °C conditions. The result suggested that Q3 in the AmDUF1517 gene promoter could be a new source of induced promoters for abiotic resistance breeding in plant genetic engineering.Introduction As a consequence of their small size, high stability and high affinity, single domain antibody fragments (sdAbs) are appealing targeting vectors for radiopharmaceutical development. With sdAbs binding to internalizing receptors like HER2, residualizing prosthetic agents can enhance tumor retention of radioiodine, which until now has been done with random labeling approaches. Herein we evaluate a site-specific strategy utilizing a radioiodinated, residualizing maleimido moiety and the anti-HER2 sdAb 5F7 bearing a GGC tail for conjugation. Methods Maleimidoethyl 3-(guanidinomethyl)-5-iodobenzoate ([131I]MEGMB) and its N-succinimidyl ester analogue, iso-[125I]SGMIB, were labeled by halodestannylation and conjugated with 5F7GGC and 5F7, respectively. Radiochemical purity, immunoreactivity and binding affinity were determined. Paired-label experiments directly compared iso-[125I]SGMIB-5F7 and [131I]MEGMIB-5F7GGC with regard to internalization/residualization and affinity on HER2-expressing SKOV-3 ovarlar tumor targeting as iso-[125I]SGMIB-5F7 but with generally lower normal tissue uptake. Advances in knowledge and implication for patient care The site specific nature of the [131I]MEGMIB reagent may facilitate clinical translation, particularly for sdAb with compromised affinity after random labeling.Introduction Primary thyroid gland malignant teratomas are extremely rare and can pose diagnostic challenges on fine needle aspiration (FNA) due to their cytomorphologic heterogeneity. Recent next generation sequencing studies have identified recurrent DICER1 hotspot mutations in these tumors, suggesting that malignant teratomas of the thyroid should be considered a distinct pathological entity. Herein, we review the clinico-radiologic and FNA findings in a series of DICER1 mutated malignant teratomas. Methods We performed a retrospective case review of 9 FNAs from 5 patients with a histologically confirmed malignant teratoma of the thyroid gland from 2 large tertiary care pathology practices. Results The patients included 4 females and 1 male, with an average age of 43 years (22-65 years). The nodules were centered within the thyroid gland and ranged from 1.7 to 10 cm in diameter. FNAs of primary thyroid teratomas demonstrate marked cellularity, epithelial proliferations, an absence of colloid, and a predominance of immature spindled cells, representing the mesenchymal and neural ectodermal components of these tumors. The FNA interpretations ranged from atypia of undetermined significance to overtly malignant. Three patients died of their disease and 2 are alive with no evidence of disease. Conclusions Malignant thyroid teratoma is a rare entity with cytomorphologic overlap with other high-grade neoplasms of the thyroid. Recent molecular studies have defined recurrent DICER1 mutations in malignant thyroid teratomas and propose these as a distinct clinicopathological entity. The features described here may be helpful in providing a correct prospective interpretation.Background Primary carnitine deficiency (PCD) is a rare but potentially life-threatening genetic disorder if left untreated. Although some patients remain asymptomatic lifelong, a few patients present with hepatic encephalopathy, hypoglycemia, cardiomyopathy, dysrhythmia, and even sudden death. Case report A 25-year-old woman with PCD collapsed suddenly while eating lunch. Bystander cardiopulmonary resuscitation (CPR) was performed for 8 min, with automated external defibrillation once before admission. Upon arrival at our emergency department (ED), she was unresponsive without a pulse or spontaneous breathing. The initial heart rhythm on the electrocardiogram monitor was ventricular fibrillation (VF). The medical staff continued CPR with defibrillation for sustained VF. Return of spontaneous circulation (ROSC) was achieved after a total resuscitation time of 14 min, with defibrillation twice after cardiac arrest. The heart rhythm after ROSC was atrial fibrillation, with a rapid ventricular rate initially and subsequent progression to sinus tachycardia with diffuse ST segment depression and a prolonged QT interval. Her low carnitine level was consistent with her underlying disease. Cardiac magnetic resonance imaging and sonography for detection of cardiomyopathy showed no significant findings. With carnitine supplementation for a few days, her plasma carnitine level returned to 30 μM, with no recurrence of ventricular dysrhythmia. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? PCD is rare but could be life-threatening, and compiling detailed histories may help emergency physicians to determine the cause of sudden cardiac death after resuscitation. This information may be used to correct potential underlying problems and prevent recurrence of the condition after treatment.Cognitive control, the ability to use goal-directed information to guide behaviour, is impaired in schizophrenia, and mainly related to dysfunctions within the fronto-posterior brain network. However, cognitive control is a broad cognitive function encompassing distinct sub-processes that, until now, studies have failed to separate and relate to specific brain regions. The goal of this preliminary fMRI study is to investigate the functional specialization of posterior brain regions, and their functional interaction with lateral prefrontal cortex (LPFC) regions, in schizophrenia. Fourteen healthy participants and 15 matched schizophrenic patients participated in this fMRI study. We used a task paradigm that differentiates two cognitive control sub-processes according to the temporal framing of information, namely the control of immediate context (present cues) vs. temporal episode (past instructions). We found that areas activated during contextual and episodic controls were in dorsal posterior regions and that activations did not significantly differ between schizophrenic patients and healthy participants.