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Abstract An Agrobacterium-mediated transformation system with glyphosate selection has been developed for the large-scale production of transgenic plants. The system uses 4-day precultured immature embryos as explants. A total of 30 vectors containing the 5-enol-pyruvylshikimate-3-phosphate synthase gene from Agrobacterium strain CP4 (aroA:CP4), which confers resistance to glyphosate, were introduced into wheat using this system. The aroA:CP4 gene served two roles in this study--selectable marker and gene of interest. More than 3,000 transgenic events were produced with an average transformation efficiency of 4.4%. The entire process from isolation of immature embryos to production of transgenic plantlets was 50-80 days. Transgenic events were evaluated over several generations based on genetic, agronomic and molecular criteria. Forty-six percent of the transgenic events fit a 3:1 segregation ratio. Molecular analysis confirmed that four of six lead transgenic events selected from Agrobacterium transformation contained a single insert and a single copy of the transgene. Stable expression of the aroA:CP4 gene was confirmed by ELISA through nine generations. A comparison of Agrobacterium-mediated transformation to a particle bombardment system demonstrated that the Agrobacterium system is reproducible, has a higher transformation efficiency with glyphosate selection and produces higher quality transgenic events in wheat. One of the lead events from this study, no. 33391, has been identified as a Roundup Ready wheat commercial candidate. [ABSTRACT FROM AUTHOR]

In this work, Trujillo melons were harvested across three years (2011–2013) in La Mancha region. Instrumental and sensory analysis were used for studying Trujillo melons. Solid phase extraction (SPE) was used for isolating free aroma compounds, and then, they were analysed by gas chromatography coupled with mass spectrometry (GC/MS). Fifty-five (55) volatile compounds were identified and quantified in La Mancha Trujillo melons over this three-year period. Experienced tasters evaluated the sensory profile of Trujillo melons, and it was characterized by jam/marmalade, cucumber, fresh fruit, sweet, green, honey and ripe fruit aroma descriptors and sweet, honey, jam/marmalade, cucumber, fresh fruit ripe fruit, spice and green flavour by mouth descriptors. This study represents the first complete aromatic characterization of Trujillo melons from La Mancha region. The obtained data suggested that these melons presented a great aromatic profile and that they represent a viable alternative for expanding the traditional market.

Treatment with covalent Bruton tyrosine kinase inhibitors (BTKi) represents an important advance in the management of relapsed or refractory mantle cell lymphoma, but these treatments are not curative and many patients ultimately relapse. Pirtobrutinib, a highly selective, noncovalent (reversible) BTKi, inhibits both wild type and C481-mutant BTK with equal low nM potency, and has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval regardless of intrinsic rate of BTK turnover. Pirtobrutinib is well tolerated and has demonstrated promising efficacy in patients with poor prognosis B-cell malignancies following prior therapy, including covalent BTKi. This phase III, head-to-head, randomized study (NCT04662255) will evaluate whether pirtobrutinib is superior to investigator's choice of covalent BTKi in patients with previously treated, BTKi-naive mantle cell lymphoma.

Thyroid screening is recommended during pregnancy with serum thyrotropin (TSH) as the primary test. However, since human chorionic gonadotropin, the serum hallmark of pregnancy, has TSH-like effects, the adequacy of TSH as a screening tool in this constellation requires further study. This study aimed to evaluate the relationship between TSH and thyroid hormones during pregnancy in order to determine if TSH is an adequate screening tool. This was a retrospective study utilizing the Clalit Health Service, Jerusalem district database between 2006-2017 in which we analyzed TSH, FT4 and FT3 measurements from 32430 pregnancies resulting in live birth. We grouped FT4 and FT3 levels by trimester and by the following TSH levels: (1) below 0.1/0.2/0.3 mIU/l, (2) 0.1-2.5/0.2-3.0/0.3-3.0 mIU/l, (3) 2.6-4.0/3.1-4.0 mIU/l, (4) 4.1-10.0 mIU/l and (5) above 10.0 mIU/l. In the first trimester, the most important for fetal brain development, FT3 was below normal, defined as below the 2.5th percentile for the population, in only 15.3% of tests with TSH over 10 mIU/l. FT4 was below normal in only 12.8% of such tests. Similar findings were noted for the second and third trimesters. As expected, there were far less abnormal tests when lower TSH cutoff levels were tested. In conclusion, TSH levels beyond the range accepted as normal do not, in most cases, reflect abnormal thyroid hormone levels during pregnancy. TSH is not a good screen for overt hypothyroidism in pregnancy. This may be due, at least in the first trimester, to thyrotropic effects of HCG., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

This study describes three closely related proteins, cloned from Brevibacillus laterosporus strains, that are lethal upon feeding to Diabrotica virgifera virgifera LeConte, the western corn rootworm (WCR). Mpp75Aa1, Mpp75Aa2 and Mpp75Aa3 were toxic to WCR larvae when fed purified protein. Transgenic plants expressing each mMpp75Aa protein were protected from feeding damage and showed significant reduction in adult emergence from infested plants by both susceptible and Cry3Bb1 and Cry34Ab1/Cry35Ab1-resistant WCR. These results demonstrate that proteins from B. laterosporus are as efficacious as the well-known Bacillus thuringiensis ( Bt ) insecticidal proteins in controlling major insect pests such as WCR. The deployment of transgenic maize expressing mMpp75Aa along with other active molecules lacking cross-resistance have the potential to be a useful tool for control of WCR populations resistant to current Bt traits. IMPORTANCE Insects feeding on roots of crops can damage the plant roots resulting in yield loss due to poor water and nutrient uptake and plant lodging. In maize the western corn rootworm (WCR) can cause severe damage to the roots resulting in significant economic loss for farmers. Genetically modified (GM) expressing Bacillus thuringiensis ( Bt ) insect control proteins, has provided a solution for control of these pests. In recent years populations of WCR resistant to the Bt proteins in commercial GM maize have emerged. There is a need to develop new insecticidal traits for the control of WCR populations resistant to current commercial traits. New proteins with commercial level efficacy on WCR from sources other than Bt are becoming more critical. The Mpp75Aa proteins, from B. laterosporus , when expressed in maize, are efficacious against the resistant populations of WCR and have the potential to provide solutions for control of resistant WCR., (Copyright © 2020 Bowen et al.)

The present work describes a density-functional theory (DFT) study of TlReO 4 in combination with powder x-ray diffraction experiments as a function of temperature and Raman measurements at ambient temperature. X-ray diffraction measurements reveal three different structures as a function of temperature. A monoclinic structure (space group P2 1 /c) is observed at room temperature while two isostructural tetragonal structures (space group I4 1 /a) are found at low- and high-temperature. In order to complement the experimental results first-principles DFT calculations were performed to compute the structural energy differences. From the total energies it is evident that the monoclinic structure has the lowest total energy when compared to the orthorhombic structure, which was originally proposed to be the structure at room temperature, which agrees with our experiments. The structural and vibrational properties of the low- and room-temperature phase of TlReO 4 have been calculated using DFT. Inclusion of van der Waals correction to the standard DFT exchange correlation functional is found to improve the agreement with the observed structural and vibrational properties. The Born effective charge of these phases has also been studied which shows a combination of ionic and covalent nature, resembling metavalent bonding. Calculations of zone-center phonon frequencies lead to the symmetry assignment of previously reported low-temperature Raman modes. We have determined the frequencies of the eight infrared-active, 13 Raman-active and three silent modes of low-temperature TlReO 4 along with 105 infrared-active and 108 Raman-active modes for room-temperature TlReO 4 . Phonons of these two phases of TlReO 4 are mainly divided into three regions which are below 150 cm -1 due to vibration of whole crystal, 250 to 400 cm -1 due to wagging, scissoring, rocking and twisting and above 900 cm -1 due to stretching in ReO 4 tetrahedron. The strongest infrared peak is associated to the internal asymmetric stretching of ReO 4 whereas the strongest Raman peak is associated to the internal symmetric stretching of ReO 4 . We have also measured the room-temperature Raman spectra of monoclinic TlReO 4 identifying up to 28 modes. This Raman spectrum has been interpreted by comparison with the previously reported Raman frequencies of the low-temperature phase and our calculated Raman frequencies of low- and room-temperature phases of TlReO 4 .

The Western corn rootworm (WCR) Diabrotica virgifera virgifera LeConte is one of the most economically important insect pests in North America. Since 2003, transgenic maize expressing WCR-active proteins from Bacillus thuringiensis (Bt) have been widely adopted as the main approach to controlling WCR in the U.S. However, the emergence of field resistance to the Bt proteins in current commercial products has been documented in recent years, highlighting the need to develop additional tools for controlling this devasting pest. Here we report the discovery of Vpb4Da2 (initially assigned as Vip4Da2), a new insecticidal protein highly selective against WCR, through high-throughput genome sequencing of a Bt strain sourced from grain dust samples collected in the eastern and central regions of the US. Vpb4Da2 contains a sequence and domain signature distinct from families of other WCR-active proteins. Under field conditions, transgenic maize expressing Vpb4Da2 demonstrates commercial-level (at or below NIS 0.25) root protection against WCR, and reduces WCR beetle emergence by ≥ 97%. Our studies also conclude that Vpb4Da2 controls WCR populations that are resistant to WCR-active transgenic maize expressing Cry3Bb1, Cry34Ab1/Cry35Ab1 (reassigned as Gpp34Ab1/Tpp35Ab1), or DvSnf7 RNA. Based on these findings, Vpb4Da2 represents a valuable new tool for protecting maize against WCR., Competing Interests: Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. Author’s employment by Bayer does not alter our adherence to PLOS ONE policies on sharing data and materials.

The structures of the six perrhenates (AReO4 A = Ag, Na, K, Rb, Cs and Tl) at room temperature have been established using powder neutron diffraction methods. These demonstrate the rigid nature of the ReO4 tetrahedra, with the Re-O distances decreasing very slightly and the O-Re-O bond angles approaching the regular tetrahedron value of 109.5° as the size of the A-type cation increases. Variable temperature synchrotron X-ray diffraction measurements show that RbReO4 undergoes a I41/a to I41/amd transition near 650 K that is associated with a change in the orientation of the ReO4- tetrahedra about the scheelite b-axis associated with a Γ3+ mode. CsReO4 has an orthorhombic pseudo scheelite structure at room temperature with rotation of the ReO4 tetrahedra about the c-axis described by mode M4+ and this undergoes a first order orthorhombic to tetragonal (Pnma to I41/a) transition near 450 K with a transition to the I41/amd structure occurring above this. TlReO4 is a rare example of a crystalline material displaying a re-entrant phase transition; 141/a to P21/c to 141/a. The monoclinic structure can be described as a scheelite superstructure that contains an ordering of tetrahedral rotations around the c-axis and along the b-axis with the irrep Γ3+ and M4+ both present. This behaviour is different to that described recently for the analogous Tc oxide TlTcO4, which highlights the differences in the chemistry of these two systems.

In euthyroidism, as thyroid Stimulating hormone (TSH) levels increase, the free triiodothyronine (FT3) to free thyroxine (FT4) ratio increases. The aim of this study was to assess if beyond the euthyroid range of TSH levels FT3/FT4 ratio continues to increase and if levothyroxine treatment reduces this ratio, possibly through TSH suppression. This cross sectional retrospective study included a total of 77 832 patients [age 22.76±15.17 years (4 days to 112 years)] evaluated and treated in community clinics between January 2009 and September 2013. Blood samples drawn in community clinics for which TSH, FT4, FT3, age, and gender were available were included. Tests with TSH below 0.5 IU/l were excluded as were samples taken during pregnancy. The FT3/FT4 ratio continued to increase significantly even with TSH above 50 mIU/l (p for trend<0.001) with an increase of more than 50% over the entire TSH range. With increasing age and female gender, the phenomenon was less prominent (p<0.001). Levothyroxine treated patients had significantly lower FT3/FT4 ratios in comparison to untreated patients up to TSH levels of 5.0 mIU/l. In conclusion, increasing TSH increases FT3/FT4 ratio even with severe hypothyroidism, less so with aging. With levothyroxine therapy, a ratio similar to untreated patients is achieved at TSH of above 5.0 mIU/l. Since T3 suppresses TSH better than T4, administration of T3 would likely normalize the FT3/FT4 ratio at a lower, ostensibly more physiological, TSH level. This could be seen as a rationale for add-on T3 therapy., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Normal changes in free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels over the lifespan and differences between sexes are not well documented, mainly because even the largest-scale studies available include relatively small cohorts. The aim of this study was to define age-related trends including sex differences based on reliable data., Methods: A large database including serum thyroid tests drawn in community clinics was studied. FT3, FT4, and TSH levels from 527,564 sera samples taken from patients age 1 year or greater were included. After highly extensive exclusion criteria applied to remove all samples that may have been taken from unhealthy people, 27,940 samples remained. These were stratified by decades of age and by sex., Results: FT3 decreases throughout life, significantly more so among females, with equalization between sexes with greater age. FT4 declines to a lesser extent, also more among females than among males. Among the very old, females have higher levels of FT4. In contrast, TSH declines until age 50 and then increases slightly in both sexes., Conclusion: This study provides reliable data regarding trends in hormonal levels by age and sex, with the major finding being higher FT3 in males throughout life except in the very young and very old. These results have important implications for diagnosing and treating thyroid conditions., Abbreviations: ANOVA = analysis of variance; BMI = body mass index; FT3 = free triiodothyronine; FT4 = free thyroxine.

Introduction: Most existing measures of oral health focus solely on negative oral health, illness, and deficiencies and ignore positive oral health. In an attempt to commence exploration of this challenging field, an innovative instrument was developed, the "Positive Oral Health and Well-Being" (POHW) index. This study aimed to validate this instrument and to explore an initial model of the pathway between oral health attributes and positive oral health., Methods: A cross-sectional, multicenter study (Israel, USA, and Germany), was conducted. Our conceptual model suggests that positive oral health attributes, which integrate with positive unawareness or positive awareness on the one hand and with positive perception on the other hand, may result via appropriate oral health behavior on positive oral health. The 17-item self-administered index was built on a theoretical concept by four experts from Israel and Germany. Reliability, factor, and correlation analyses were performed. For external correlations and to measure construct validity of the instrument, we utilized the oral health impact profile-14, self-perceived oral impairment, life satisfaction, self-perceived well-being, sociodemographic and behavioral data, and oral health status indices., Results: Four hundred and seventy participants took part in our three-center study. The combined data set reliability analyses detected two items which were not contributing to the index reliability. Thus, we tested a 15-item construct, and a Cronbach's α value of 0.933 was revealed. Primary factor analysis of the whole sample indicated three subconstructs which could explain 60 % of variance. Correlation analyses demonstrated that the POHW and OHIP-14 were strongly and negatively associated. The POHW correlated strongly and positively with general well-being, moderately with life satisfaction, and weakly with the perceived importance of regular dental checkups. It correlated moderately and negatively with perceived oral impairment, and marginally and negatively with dental caries experience (DMFT) and periodontal health status (CPI) scores. When DMFT and CPI clinical measurements were categorized, a higher score of POHW was revealed for better oral health., Discussion: Our study introduced a new instrument with good reliability and sound correlations with external measures. This instrument is the first to allow measurability of positive instead of impaired oral health. We utilized subjective-psychological and functional-social measures. The current results indicate that by further exploring our conceptual model, POHW may be of importance for identifying patients with good and poor oral health, and building an effective and inexpensive strategy for prevention, by being able to evaluate the effect of interventions in a standardized way.

An Agrobacterium-mediated transformation system with glyphosate selection has been developed for the large-scale production of transgenic plants. The system uses 4-day precultured immature embryos as explants. A total of 30 vectors containing the 5-enol-pyruvylshikimate-3-phosphate synthase gene from Agrobacterium strain CP4 (aroA:CP4), which confers resistance to glyphosate, were introduced into wheat using this system. The aroA:CP4 gene served two roles in this study-selectable marker and gene of interest. More than 3,000 transgenic events were produced with an average transformation efficiency of 4.4%. The entire process from isolation of immature embryos to production of transgenic plantlets was 50-80 days. Transgenic events were evaluated over several generations based on genetic, agronomic and molecular criteria. Forty-six percent of the transgenic events fit a 3:1 segregation ratio. Molecular analysis confirmed that four of six lead transgenic events selected from Agrobacterium transformation contained a single insert and a single copy of the transgene. Stable expression of theAROA:CP4 gene was confirmed by ELISA through nine generations. A comparison of Agrobacterium-mediated transformation to a particle bombardment system demonstrated that the Agrobacterium system is reproducible, has a higher transformation efficiency with glyphosate selection and produces higher quality transgenic events in wheat. One of the lead events from this study, no. 33391, has been identified as a Roundup Ready wheat commercial candidate.

While surgery and radiation therapy remain the only definitive treatments for prostate cancer, single modality therapy has been associated with high failure rates in patients with aggressive disease. Although hormonal therapy has been effective in cases of metastatic disease, the timing of treatment with respect to definitive therapy remains controversial. This review will explore the efficacy of hormonal and chemotherapy in both the adjuvant and neoadjuvant settings. A MEDLINE search was performed to identify pertinent articles regarding both adjuvant and neoadjuvant therapy in prostate cancer. Articles of historical relevance in addition to those using large patient numbers with a randomized design were reviewed preferentially. Since hormonal therapy has been considered standard treatment at the time of cancer progression after definitive therapy, many of the randomized trials essentially compared adjuvant therapy to delayed therapy. Historical trials using adjuvant hormonal therapy have been limited due to difficulties in clinical staging, as well as toxicities attributed to the formulations used. More recently, hormonal therapy has been found to delay disease progression, increase disease-free survival, and decrease mortality when given immediately after prostatectomy or radiation therapy in selected patients. Neoadjuvant hormonal therapy can improve disease-free survival and local control when given before radiation therapy; it has only decreased positive surgical margins when given prior to radical prostatectomy. Although hormonal therapy given immediately after either radical prostatectomy or radiation therapy is highly effective, the side effects of persistent long-term use must be weighed for each patient. While the use of chemotherapy has been limited by the lack of active agents, newer combinations have shown effectiveness in patients with hormone refractory disease, raising the possibility of their use in the adjuvant setting.

The AIDS pandemic throughout the world, and particularly in Thailand, is not just a physical disease that has evaded much of our control. It is symptomatic of a chronic, more pervasive and sinister plague that governs modern societies. This plague is social and political in nature. In the case of Thailand's AIDS pandemic, this paper argues that the underlying sociopolitical plague that further aggravates the AIDS crisis may be found in the internal contradictions that govern the Thai sex industry and its comodification of women and sex. It further suggests that current Thai management of the AIDS pandemic, though effective in terms of increasing the public's awareness about AIDS, its transmission modes and preventive measures, is less effective in the long run, because it fails to adequately address structural formations, contradictions, and practices that constitute and reproduce the Thai sex industry. Two objectives are attempted in this paper: first, a dialectical analysis of the internal contradictions in Thai society, as it relates to the sex industry, the family, and Buddhist institutions in Thailand; and, second, a line of response to the AIDS pandemic in Thailand.

Purified particles of barley yellow dwarf luteovirus (BYDV) contain a major 22-kDa protein and a minor protein of approximately 58 kDa. The 22-kDa capsid protein is encoded by open reading frame (ORF) 3. ORF 5 is immediately downstream and in frame with ORF 3 and a 72-kDa protein can be translated via a readthrough suppression of the ORF 3 termination codon. Antibodies were produced against two Escherichia coli expressed polypeptides that represent the amino- and carboxyl-terminal halves of a putative 50-kDa protein encoded by ORF 5. Immunological analyses indicated that the 58-kDa protein associated with purified virions contained sequences encoded by ORF 3 and ORF 5. The carboxyl terminal portion of the full-length (72 kDa) readthrough protein was absent from the 58-kDa protein. The full-length readthrough protein was detected in infected oat protoplasts and plant tissue, but was not associated with virus particles purified from plants. The carboxyl-terminal portion of the 72-kDa readthrough protein was not required for aphid transmission; however, virus was transmitted more efficiently from protoplast extracts containing virions and soluble 72-kDa readthrough protein than from mock-inoculated protoplast extracts to which plant purified virus was added. The full-length readthrough protein, although not required for transmission, may increase the transmission efficiency of BYDV by aphids.