Spider silk has extraordinary mechanical properties, displaying high tensile strength, elasticity, and toughness. Given the high performance of natural fibers, one of the long-term goals of the silk ...community is to manufacture large-scale synthetic spider silk. This process requires vast quantities of recombinant proteins for wet-spinning applications. Attempts to synthesize large amounts of native size recombinant spidroins in diverse cell types have been unsuccessful. In these studies, we design and express recombinant miniature black widow MaSp1 spidroins in bacteria that incorporate the N-terminal and C-terminal domain (NTD and CTD), along with varying numbers of codon-optimized internal block repeats. Following spidroin overexpression, we perform quantitative analysis of the bacterial proteome to identify proteins associated with spidroin synthesis. Liquid chromatography with tandem mass spectrometry (LC MS/MS) reveals a list of molecular targets that are differentially expressed after enforced mini-spidroin production. This list included proteins involved in energy management, proteostasis, translation, cell wall biosynthesis, and oxidative stress. Taken together, the purpose of this study was to identify genes within the genome of
for molecular targeting to overcome bottlenecks that throttle spidroin overexpression in microorganisms.
ABSTRACT
We present 11 detections of FRB 121102 in ∼3 h of observations during its ‘active’ period on the 10th of 2019 September. The detections were made using the newly deployed MeerTRAP system and ...single pulse detection pipeline at the MeerKAT radio telescope in South Africa. Fortuitously, the Nançay radio telescope observations on this day overlapped with the last hour of MeerKAT observations and resulted in four simultaneous detections. The observations with MeerKAT’s wide band receiver, which extends down to relatively low frequencies (900–1670 MHz usable L-band range), have allowed us to get a detailed look at the complex frequency structure, intensity variations, and frequency-dependent sub-pulse drifting. The drift rates we measure for the full-band and sub-banded data are consistent with those published between 600 and 6500 MHz with a slope of −0.147 ± 0.014 ms−1. Two of the detected bursts exhibit fainter ‘precursors’ separated from the brighter main pulse by ∼28 and ∼34 ms. A follow-up multi-telescope campaign on the 6th and 8th of 2019 October to better understand these frequency drifts and structures over a wide and continuous band was undertaken. No detections resulted, indicating that the source was ‘inactive’ over a broad frequency range during this time.
Workup of incidental thyroid nodules detected on CT imaging could be contributing to the increased diagnosis of small thyroid cancers. The purpose of this study was to evaluate recent trends in the ...incidence of thyroid cancer, and to determine the relationship between annual CT imaging volume and rate of thyroid cancer diagnosis.
This retrospective cohort study used data bases for thyroid cancer and CT imaging volume. Thyroid cancer data from 1983-2009 were obtained from the Surveillance, Epidemiology, and End Results data base. National Council of Radiation Protection and Measurements Report No. 160 provided data on hospital and nonhospital CT imaging volume for 1993-2006. Trends in thyroid cancer were modeled for overall incidence on the basis of patient age, tumor histologic features, and tumor size and stage. Linear regression analysis was performed to evaluate the strength of the relationship between annual CT scan volume and the incidence of thyroid cancer by tumor size and histologic type.
In 2009, the incidence of thyroid cancer was 14 per 100,000, which represented a 1.9-fold increase compared with 2000. The growth in incidence was exponential compared with a minimal linear increase in thyroid cancer mortality rate. The subgroup with the greatest change was subcentimeter papillary carcinoma, with doubling in incidence approximately every 6.2 years. The linear relationship between annual CT scan volume and the incidence of subcentimeter papillary carcinoma was very strong (R(2) = 0.98; P < .0001).
The incidence of subcentimeter papillary carcinoma is growing at an exponential rate without significant change in mortality rate. The strong linear relationship between new cases of subcentimeter papillary carcinomas and the number of CT scans per year suggests that an increase in CT scans may increase the detection of incidental thyroid cancers.
There are no guidelines for reporting incidental thyroid nodules seen on CT and MR imaging. We evaluated radiologists' current reporting practices for incidental thyroid nodules detected on these ...imaging modalities.
Radiologists were surveyed regarding their reporting practices by using 14 scenarios of incidental thyroid nodules differing in size, patient demographics, and clinical history. Scenarios were evaluated for the following: 1) radiologists' most commonly selected response, and 2) the proportion of radiologists selecting that response (degree of agreement). These measures were used to determine how the patient scenario and characteristics of the radiologists affected variability in practice.
One hundred fifty-three radiologists participated. In 8/14 scenarios, the most common response was to "recommend sonography." For the other scenarios, the most common response was to "report in only body of report." The overall mean agreement for the 14 scenarios was 53%, and agreement ranged from 36% to 75%. Smaller nodules had lower agreement: 43%-51% for 8-mm nodules compared with 64%-75% for 15-mm nodules. Agreement was poorest for the 10-mm nodule in a 60-year-old woman (36%) and for scenarios with additional history of lung cancer (39%) and multiple nodules (36%). There was no significant difference in reporting practices and agreement when radiologists were categorized by years of practice, practice type, and subspecialty (P > .55).
The reporting practice for incidental thyroid nodules on CT or MR imaging is highly variable among radiologists, especially for patients with smaller nodules (≤10 mm) and patients with multiple nodules and a history of cancer. This variability highlights the need for practice guidelines.
The "polar vessel" sign has been previously described on sonography of parathyroid adenomas. We estimated the 4D CT prevalence of the polar vessel sign and determined features of parathyroid adenomas ...that are associated with this sign.
Twenty-eight consecutive patients with parathyroid adenomas underwent 4D CT between 2008 and 2012 at 2 institutions. 4D CT images were reviewed for the presence of the polar vessel sign and a second vascular finding of an enlarged ipsilateral inferior thyroid artery. The polar vessel sign was correlated with adenoma weight and size and arterial phase CT attenuation.
Thirty-two parathyroid adenomas in 28 patients were studied, with a mean adenoma weight of 0.66 ± 0.65 g, a mean maximal CT diameter of 11.1 ± 4.9 mm, and a mean arterial attenuation of 148 ± 47 HU. The polar vessel sign was seen in 20/32 (63%) adenomas. Adenomas with a polar vessel had higher arterial phase attenuation than adenomas without a polar vessel (163 and 122 HU, respectively, P < .01). Size and weight were not significantly different for adenomas with and without polar vessels. An enlarged inferior thyroid artery was seen in only 2/28 (7%) patients with unilateral disease.
The polar vessel sign was present in nearly two-thirds of parathyroid adenomas on 4D CT and was more likely to be present in adenomas that had greater arterial phase enhancement. This sign can be used along with enhancement characteristics to increase the radiologist's confidence that a visualized lesion is a parathyroid adenoma rather than a thyroid nodule or lymph node.
Thyroid nodules are common incidental findings on CT, but there are no clear guidelines regarding their further diagnostic work-up. This study compares the performance of 2 risk-categorization ...methods of selecting CT-detected incidental thyroid nodules for work-up.
The 2 categorization methods were method A, based on nodule size ≥10 mm, and method B, a 3-tiered system based on aggressive imaging features, patient age younger than 35 years or nodule size of ≥15 mm. In part 1, the 2 categorization methods were applied to thyroid cancers in the SEER data base of the National Cancer Institute to compare the cancer capture rates and survival. In part two, 755 CT neck scans at our institution were retrospectively reviewed for the presence of ITNs of ≥5 mm, and the same 2 categorization methods were applied to the CT cases to compare the number of patients who would theoretically meet the criteria for work-up. Comparisons of proportions of subjects captured under methods A and B were made by using the McNemar test.
For 84,720 subjects in the SEER data base, methods A and B each captured 74% (62,708/84,720 and 62,586/84,720, respectively) of malignancies. SEER subjects who would not have met the criteria for further work-up by both methods had equally excellent 10-year cause-specific and relative survival of >99%. For part 2, the prevalence of ITNs of ≥5 mm at our institution was 133/755 (18%). The number of ITNs that would be recommended for work-up by method A was 57/133 (43%) compared with 31/133 (23%) for method B (P < .0005).
Compared with using a 10-mm cutoff, the 3-tiered risk-stratification method identified fewer ITNs for work-up but captured the same proportion of cancers in a national data base and showed no difference in missing high-mortality cancers.
The islet in type 2 diabetes is characterized by β-cell loss, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). When protein misfolding protective ...mechanisms are overcome, human IAPP (h-IAPP) forms membrane permeant toxic oligomers that induce β-cell dysfunction and apoptosis. In humans with type 2 diabetes (T2D) and mice transgenic for h-IAPP, endoplasmic reticulum (ER) stress has been inferred from nuclear translocation of CCAAT/enhancer-binding protein homologous protein (CHOP), an established mediator of ER stress. To establish whether h-IAPP toxicity is mediated by ER stress, we evaluated diabetes onset and β-cell mass in h-IAPP transgenic (h-TG) mice with and without deletion of CHOP in comparison with wild-type controls. Diabetes was delayed in h-TG CHOP−/− mice, with relatively preserved β-cell mass and decreased β-cell apoptosis. Deletion of CHOP attenuates dysfunction of the autophagy/lysosomal pathway in β-cells of h-TG mice, uncovering a role for CHOP in mediating h-IAPP-induced dysfunction of autophagy. As deletion of CHOP delayed but did not prevent h-IAPP-induced β-cell loss and diabetes, we examined CHOP-independent stress pathways. JNK, a target of the IRE-1pTRAF2 complex, and the Bcl-2 family proapoptotic mediator BIM, a target of ATF4, were comparably activated by h-IAPP expression in the presence and absence of CHOP. Therefore, although these studies affirm that CHOP is a mediator of h-IAPP-induced ER stress, it is not the only one. Therefore, suppression of CHOP alone is unlikely to be a durable therapeutic strategy to protect against h-IAPP toxicity because multiple stress pathways are activated.
Multigland disease represents a challenging group of patients with primary hyperparathyroidism. Additional lesions may be missed on imaging because they are not considered or are too small to be ...seen. The aim of this is study was to identify 4D-CT imaging and biochemical predictors of multigland disease.
This was a retrospective study of 155 patients who underwent 4D-CT and successful surgery with a biochemical cure that compared patients with multigland and single-gland disease. Variables studied included the size of the largest lesion on 4D-CT, the number of lesions prospectively identified on 4D-CT, serum calcium levels, serum parathyroid hormone levels, and the Wisconsin Index (the product of serum calcium and parathyroid hormone levels). Imaging findings and the Wisconsin Index were used to calculate a composite multigland disease scoring system. We evaluated the predictive value of individual variables and the scoring system for multigland disease.
Thirty-six patients with multigland disease were compared with 119 patients with single-gland disease. Patients with multigland disease had significantly lower Wisconsin Index scores, smaller lesion size, and a higher likelihood of having either multiple or zero lesions identified on 4D-CT (P ≤ .01). Size cutoff of <7 mm had 85% specificity for multigland disease, but including other variables in the composite multigland disease score improved the specificity. Scores of ≥4, ≥5, and 6 had specificities of 81%, 93%, and 98%, respectively.
The composite multigland disease scoring system based on 4D-CT imaging findings and biochemical data can identify patients with a high likelihood of multigland disease. Communicating the suspicion for multigland disease in the radiology report could influence surgical decision-making, particularly when considering re-exploration in a previously operated neck or initial limited neck exploration.
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