Introgression of the bread wheat D genome encoded Lr34/Yr18/Sr57/Pm38/Ltn1 adult plant resistance gene into Triticum turgidum (durum wheat).

KEY MESSAGE: Lack of function of a D-genome adult plant resistance gene upon introgression into durum wheat. The wheat Lr34/Yr18/Sr57/Pm38/Ltn1 adult plant resistance gene (Lr34), located on chromosome arm 7DS, provides broad spectrum, partial, adult plant resistance to leaf rust, stripe rust, stem rust and powdery mildew. It has been used extensively in hexaploid bread wheat (AABBDD) and conferred durable resistance for many decades. These same diseases also occur on cultivated tetraploid durum wheat and emmer wheat but transfer of D genome sequences to those subspecies is restricted due to very limited intergenomic recombination. Herein we have introgressed the Lr34 gene into chromosome 7A of durum wheat. Durum chromosome substitution line Langdon 7D(7A) was crossed to Cappelli ph1c, a mutant derivative of durum cultivar Cappelli homozygous for a deletion of the chromosome pairing locus Ph1. Screening of BC1F2 plants and their progeny by KASP and PCR markers, 90 K SNP genotyping and cytology identified 7A chromosomes containing small chromosome 7D fragments encoding Lr34. However, in contrast to previous transgenesis experiments in durum wheat, resistance to wheat stripe rust was not observed in either Cappelli/Langdon 7D(7A) or Bansi durum plants carrying this Lr34 encoding segment due to low levels of Lr34 gene expression.

Glycemic Control and the Weight Benefit of a Daily 7 mg Dose of Oral Semaglutide Versus an Alternate-Day 14 mg Dose of Oral Semaglutide From an Ambulatory Glucose Monitoring Data: A Retrospective Cohort Study From Eastern India.

INTRODUCTION: Oral semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) class of antidiabetic medication. High costs and GI side effects are the major limitations of its widespread use. Some patients who were on a 14 mg dose of oral semaglutide self-prescribed an alternate-day schedule to mitigate GI side effects and to reduce the cost. METHODS: This retrospective observational cohort study evaluates the ambulatory glucose profile (AGP) data, extrapolated glycosylated hemoglobin (HbA1C), and BMI of 11 types of 2 diabetes mellitus (T2DM) while they were on an alternate-day 14 mg dose of oral semaglutide compared to their record while on a daily 7 mg dose. The AGP metrics (time-in-range (TIR), time-below-range (TBR), and time-above-range (TAR)) along with extrapolated HbA1C and BMI were analyzed. Statistical analysis was done using SPSS Statistics version 21.0. RESULTS: No statistically significant difference in the AGP metrics between the AGP profile of a daily 7 mg dose and the AGP profile of an alternate-day 14 mg dose of oral semaglutide was observed. Interestingly, a statistically significant progressive decline in BMI value was observed even on the alternate-day 14 mg dose when compared to the daily 7 mg dose. CONCLUSION: In this small cohort of patients, the metrics of short-term glycemic control and the extrapolated HbA1C values were similar for the daily 7 mg dose versus the alternate-day 14 mg dose of oral semaglutide. BMI showed progressive reduction which was statistically significant even with the alternate-day 14 mg dose of oral semaglutide.

Early Insight Into the Retrospective Data of a Case Series on Type 2 Diabetes Mellitus on Alternate-Day Dosing of Oral Semaglutide: Utopia or Reality?

Introduction Oral semaglutide, with a long half-life of seven days, is the first oral-based peptide drug and is used as an antidiabetic for the reduction of glycosylated hemoglobin (HbA1c). Oral semaglutide, like other glucagon-like peptide-1 receptor agonists (GLP1RAs), is costly and has gastrointestinal (GI) side effects, especially with a 14 mg dose. In the real world, some type 2 diabetes mellitus (T2DM) patients on 14 mg oral dose adopt an alternate-day strategy to minimize unwanted GI symptoms. In this study, we analyzed the ambulatory glucose profile (AGP) data of patients with T2DM who were on 14 mg alternate-day oral semaglutide therapy. Methods This retrospective observational study evaluated the AGP data of 10 patients on alternate-day dosing of 14 mg oral semaglutide. The AGP data over a period of 14 days on a single group of patients were analyzed without any control group or randomization and are presented as a case series. AGP monitoring, using Freestyle Libre Pro (Abbott, Illinois, United States), is a standard operating procedure of the endocrinology department for all T2DM patients who were put on oral semaglutide therapy. The AGP data of the glycemic parameters time-in-range (TIR), time-above-range (TAR), and time-below-range (TBR), were compared between the days when oral semaglutide was consumed (days-on-drug) versus the days when oral semaglutide was not consumed (days-off-drug). The statistical analysis was done with Statistical Package for Social Sciences (SPSS) version 21.0 (IBM Corp., Armonk, NY). Results We applied the Shapiro-Wilk test (sample size <50) for normality testing; the TIR values of days-on-drug and days-off-drug showed high p values (p =0.285 and 0.109), respectively. This indicated that TIR values days-on-drug and days-off-drug were normally distributed. Although, the distribution of TAR and TBR values days-on-drug and days-off-drug, were not normal as they had small p values (p< 0.05). Hence, further analysis of the paired set of data was done using the Wilcoxon signed-rank test. It revealed no difference in TIR, TAR, and TBR between the two groups (days-on-drug and days-off-drug). Conclusion Throughout the period of observation, the glycemic metrics (TIR, TAR, and TBR) remained steady with a 14 mg alternate-day oral semaglutide regimen.

Haplotype variants of the stripe rust resistance gene Yr28 in Aegilops tauschii.

KEY MESSAGE: Stripe rust resistance gene YrAet672 from Aegilops tauschii accession CPI110672 encodes a nucleotide-binding and leucine-rich repeat domain containing protein similar to YrAS2388 and both these members were haplotypes of Yr28. New sources of host resistance are required to counter the continued emergence of new pathotypes of the wheat stripe rust pathogen Puccinia striiformis Westend. f. sp. tritici Erikss. (Pst). Here, we show that CPI110672, an Aegilops tauschii accession from Turkmenistan, carries a single Pst resistance gene, YrAet672, that is effective against multiple Pst pathotypes, including the four predominant Pst lineages present in Australia. The YRAet672 locus was fine mapped to the short arm of chromosome 4D, and a nucleotide-binding and leucine-rich repeat gene was identified at the locus. A transgene encoding the YrAet672 genomic sequence, but lacking a copy of a duplicated sequence present in the 3' UTR, was transformed into wheat cultivar Fielder and Avocet S. This transgene conferred a weak resistance response, suggesting that the duplicated 3' UTR region was essential for function. Subsequent analyses demonstrated that YrAet672 is the same as two other Pst resistance genes described in Ae. tauschii, namely YrAS2388 and Yr28. They were identified as haplotypes encoding identical protein sequences but are polymorphic in non-translated regions of the gene. Suppression of resistance conferred by YrAet672 and Yr28 in synthetic hexaploid wheat lines (AABBDD) involving Langdon (AABB) as the tetraploid parent was associated with a reduction in transcript accumulation.

A recombined Sr26 and Sr61 disease resistance gene stack in wheat encodes unrelated NLR genes.

The re-emergence of stem rust on wheat in Europe and Africa is reinforcing the ongoing need for durable resistance gene deployment. Here, we isolate from wheat, Sr26 and Sr61, with both genes independently introduced as alien chromosome introgressions from tall wheat grass (Thinopyrum ponticum). Mutational genomics and targeted exome capture identify Sr26 and Sr61 as separate single genes that encode unrelated (34.8%) nucleotide binding site leucine rich repeat proteins. Sr26 and Sr61 are each validated by transgenic complementation using endogenous and/or heterologous promoter sequences. Sr61 orthologs are absent from current Thinopyrum elongatum and wheat pan genome sequences, contrasting with Sr26 where homologues are present. Using gene-specific markers, we validate the presence of both genes on a single recombinant alien segment developed in wheat. The co-location of these genes on a small non-recombinogenic segment simplifies their deployment as a gene stack and potentially enhances their resistance durability.

A five-transgene cassette confers broad-spectrum resistance to a fungal rust pathogen in wheat.

Breeding wheat with durable resistance to the fungal pathogen Puccinia graminis f. sp. tritici (Pgt), a major threat to cereal production, is challenging due to the rapid evolution of pathogen virulence. Increased durability and broad-spectrum resistance can be achieved by introducing more than one resistance gene, but combining numerous unlinked genes by breeding is laborious. Here we generate polygenic Pgt resistance by introducing a transgene cassette of five resistance genes into bread wheat as a single locus and show that at least four of the five genes are functional. These wheat lines are resistant to aggressive and highly virulent Pgt isolates from around the world and show very high levels of resistance in the field. The simple monogenic inheritance of this multigene locus greatly simplifies its use in breeding. However, a new Pgt isolate with virulence to several genes at this locus suggests gene stacks will need strategic deployment to maintain their effectiveness.

The wheat Sr22, Sr33, Sr35 and Sr45 genes confer resistance against stem rust in barley.

In the last 20 years, stem rust caused by the fungus Puccinia graminis f. sp. tritici (Pgt), has re-emerged as a major threat to wheat and barley production in Africa and Europe. In contrast to wheat with 60 designated stem rust (Sr) resistance genes, barley's genetic variation for stem rust resistance is very narrow with only ten resistance genes genetically identified. Of these, only one complex locus consisting of three genes is effective against TTKSK, a widely virulent Pgt race of the Ug99 tribe which emerged in Uganda in 1999 and has since spread to much of East Africa and parts of the Middle East. The objective of this study was to assess the functionality, in barley, of cloned wheat Sr genes effective against race TTKSK. Sr22, Sr33, Sr35 and Sr45 were transformed into barley cv. Golden Promise using Agrobacterium-mediated transformation. All four genes were found to confer effective stem rust resistance. The barley transgenics remained susceptible to the barley leaf rust pathogen Puccinia hordei, indicating that the resistance conferred by these wheat Sr genes was specific for Pgt. Furthermore, these transgenic plants did not display significant adverse agronomic effects in the absence of disease. Cloned Sr genes from wheat are therefore a potential source of resistance against wheat stem rust in barley.

An Observational Study of the Quality of Life Among Gender Incongruent Individuals From "Hijra" Community of India.

BACKGROUND: The term "hijra" is used to describe eunuchs, intersex, and gender incongruent individuals from hijra community people in the Indian subcontinent. Various adversities, violence, and discrimination experienced by many of them might have adverse consequences on their quality of life (QOL). The present study was conducted to assess the QOL among adult gender incongruent individuals from the hijra community. METHODS: Data of thirty-seven hijra enrolled in the Endocrine outpatient clinic (hijra group) and thirty-seven healthy employees of the hospital (control group) were analyzed with regard to QOL. QOL was assessed by using the physical and mental health Short Form-36 (SF-36) health survey questionnaire. Results on continuous measurements were presented as mean ± SD and results on categorical measurements were presented in number and percent. Mann-Whitney U test or Student t-test was used to find the significance of study parameters between the two groups according to the data distribution. RESULTS: In the domain namely role limitation due to emotional problem, the hijra cohort had a statistically significantly lower score (66.4 ± 20.2) versus the control cohort (83.4 ± 23.7), P = 0.002. No difference was observed between two groups with regards to other QOL domains namely general health perception, physical functioning, role limitation due to physical problem, bodily pain, general mental health, social functioning, and vitality. CONCLUSIONS: QOL of the gender incongruent individuals from the hijra community included in this study and the control group comprising of hospital employees were almost similar, though the former had reported lower levels of emotional health issues than the latter.

Lives of Gender Incongruent Community: An Indian Subset Chants "All is Well".

CONTEXT: Gender incongruent individuals are exposed to unique stressors as a result of their minority social position. Poor social support has a further adverse impact on the lives and wellbeing of gender incongruent individuals. There is a paucity of scientific data from India on the socioeconomic status (SES) of gender incongruent community. AIMS: Aim of the study is to understand and estimate the social support, wellbeing, and SES of gender incongruent individuals in Eastern India. SUBJECTS AND METHODS: Data of 120 gender incongruent patients from the endocrinology outpatient department of a tertiary care hospital in eastern India were collected. We looked at demographic characteristics, social support, underlying psychiatric comorbidities, and SES. SES was calculated by the Kuppuswamy's socioeconomic status (KSS) scale based on occupation, education, and income. STATISTICAL ANALYSIS USED: Microsoft Word and Excel were used to generate tables. RESULTS: Most of the gender incongruent individuals were transfeminine. Almost half of them had no history of addiction. Most of them had good support from family and friends and very few (only 3%) had mental health problems. Calculation by KSS scale showed most of the study population lay in the upper middle or lower middle socioeconomic class. CONCLUSIONS: Strong support from friends and family appears a key factor for protection against psychiatric comorbidities and an all-round impact on the lives and wellbeing of the study population.

Intermittent bilateral coherence in physiological and essential hand tremor.

OBJECTIVE: To investigate the prevalence and the temporal structure of bilateral coherence in physiological (PT) and essential (ET) hand tremor. METHODS: Triaxial accelerometric recordings from both hands in 30 healthy subjects and 34 ET patients were analyzed using spectral coherence and wavelet coherence methods. In 12 additional healthy subjects, the relation between the hand tremor and the chest wall acceleration was evaluated using partial coherence analysis. RESULTS: The majority of both PT and ET subjects displayed significant bilateral coherence. While in PT, bilateral coherence was most frequently found in resting hand position (97% of subjects), in ET the prevalence was comparable for resting (54%) and postural (49%-57%) positions. In both PT and ET, epochs of strong coherence lasting several to a dozen seconds were separated by intervals of insignificant coherence. In PT, bilateral coherence at the main tremor frequency (8-12Hz) was coupled with the ballistocardiac rhythm. CONCLUSION: The oscillations of the two hands are intermittently synchronized in both PT and ET. We propose that in postural PT, bilateral coherence at the main tremor frequency arises from transient simultaneous entrainment of the left and right hand oscillations to ballistocardiac forcing. SIGNIFICANCE: Bilateral coherence of hand kinematics provides a sensitive measure of synchronizing influences on the left and right tremor oscillators.

Correction: independently controlled wing stroke patterns in the fruit fly Drosophila melanogaster.

[This corrects the article DOI: 10.1371/journal.pone.0116813.].

Independently controlled wing stroke patterns in the fruit fly Drosophila melanogaster.

Flies achieve supreme flight maneuverability through a small set of miniscule steering muscles attached to the wing base. The fast flight maneuvers arise from precisely timed activation of the steering muscles and the resulting subtle modulation of the wing stroke. In addition, slower modulation of wing kinematics arises from changes in the activity of indirect flight muscles in the thorax. We investigated if these modulations can be described as a superposition of a limited number of elementary deformations of the wing stroke that are under independent physiological control. Using a high-speed computer vision system, we recorded the wing motion of tethered flying fruit flies for up to 12,000 consecutive wing strokes at a sampling rate of 6250 Hz. We then decomposed the joint motion pattern of both wings into components that had the minimal mutual information (a measure of statistical dependence). In 100 flight segments measured from 10 individual flies, we identified 7 distinct types of frequently occurring least-dependent components, each defining a kinematic pattern (a specific deformation of the wing stroke and the sequence of its activation from cycle to cycle). Two of these stroke deformations can be associated with the control of yaw torque and total flight force, respectively. A third deformation involves a change in the downstroke-to-upstroke duration ratio, which is expected to alter the pitch torque. A fourth kinematic pattern consists in the alteration of stroke amplitude with a period of 2 wingbeat cycles, extending for dozens of cycles. Our analysis indicates that these four elementary kinematic patterns can be activated mutually independently, and occur both in isolation and in linear superposition. The results strengthen the available evidence for independent control of yaw torque, pitch torque, and total flight force. Our computational method facilitates systematic identification of novel patterns in large kinematic datasets.

Graphite epoxide.

Oxidation of graphite may be carried out by reaction with meta-chloroperoxybenzoic acid to yield graphite epoxide. Scanning tunneling microscopy (STM) showed that the functionalization occurs at the edges rather than on the basal plane of the graphite. Quantification of the epoxide content is possible through the deepoxidation reaction using MeReO3/PPh3.

Surface area measurement of functionalized single-walled carbon nanotubes.

Single-walled carbon nanotubes have been functionalized and the specific surface areas of the functionalized nanotubes measured. Contrary to expectations, functionalization leads to a decrease in specific surface area compared to that of the unfunctionalized nanotubes. Treatment with a concentrated 1:1 nitric/sulfuric acid mixture followed by high-temperature baking at 1000 degrees C was found to increase the specific surface area of the nanotubes. For the unfunctionalized SWNTs, this treatment increases the specific surface area (SSA) by 20%. In the case of SWNTs functionalized by n-butyl groups the increase in the SSA was nearly 2-fold with the value increasing from 410 (drying at 110 degrees C) to 770 m2/gm (acid and bake treatment followed by drying at 110 degrees C). For the ozonized SWNTs, the SSA increases more than 3-fold from 381 (drying at 110 degrees C) to 1068 m2/gm (acid and bake treatment followed by drying at 110 degrees C). SEM images indicate that the nanotubes rebundle in the solid state with an average bundle size of 10-30 nm. AFM studies show that the ozonized tubes have been cut to short bundles after ozonolysis. Hydrogen uptake studies carried out on the baked ozonized tubes led to a 3 wt % hydrogen uptake at 77 K and 30 bar.

Sequestration of drugs using poly(acrylic acid) and alkyl modified poly(acrylic acid) nanoparticles.

Poly(acrylic acid) and alkyl modified poly(acrylic acid) nanoparticles were formed by the reverse microemulsion technique. Scanning electron microspectroscopy, zeta potential measurements and fluorescence spectroscopy were used for their characterization. It was observed that they are in the range 80-100 nm and their surface charge is pH dependent. The particles were assessed for their ability to extract drugs such as amitriptyline and bupivacaine from bulk fluid for their potential application as scavengers for overdosed drugs. In normal saline (0.9% NaCl) unmodified poly(acrylic acid) nanoparticles (per gram) extracted 81 mg amitriptyline and 62 mg bupivacaine in 5 minutes, whereas for the alkyl modified poly(acrylic acid) nanoparticles, extractions were 68 mg and 51 mg amitriptyline and bupivacaine respectively per gram of nanoparticles used.

Platinum chromophore-based systems for photoinduced charge separation: a molecular design approach for artificial photosynthesis.

Photoinduced charge separation is a fundamental step in photochemical energy conversion. In the design of molecularly based systems for light-to-chemical energy conversion, this step is studied through the construction of two- and three-component systems (dyads and triads) having suitable electron donor and acceptor moieties placed at specific positions on a charge-transfer chromophore. The most extensively studied chromophores in this regard are ruthenium(II) tris(diimine) systems with a common 3MLCT excited state, as well as related ruthenium(II) bis(terpyridyl) systems. This Forum contribution focuses on dyads and triads of an alternative chromophore, namely, platinum(II) di- and triimine systems having acetylide ligands. These d8 chromophores all possess a 3MLCT excited state in which the lowest unoccupied molecular orbital is a pi orbital on the heterocyclic aromatic ligand. The excited-state energies of these Pt(II) chromophores are generally higher than those found for the ruthenium(II) tris(diimine) systems, and the directionality of the charge transfer is more certain. The first platinum diimine bis(arylacetylide) triad, constructed by attaching phenothiazene donors to the arylacetylide ligands and a nitrophenyl acceptor to 5-ethynylphenanthroline of the chromophore, exhibited a charge-separated state of 75-ns duration. The first Pt(tpy)(arylacetylide)+-based triad contains a trimethoxybenzamide donor and a pyridinium acceptor and has been structurally characterized. The triad has an edge-to-edge separation between donor and acceptor fragments of 27.95 Angstroms. However, while quenching of the emission is complete for this system, transient absorption (TA) studies reveal that charge transfer does not move onto the pyridinium acceptor. A new set of triads described in detail here and having the formula [Pt(NO2phtpy)(p-C triple-bond C-C6H4CH2(PTZ-R)](PF6), where NO2phtpy = 4'-{4-[2-(4-nitrophenyl)vinyl]phenyl}-2,2';6',2''-terpyridine and PTZ = phenothiazine with R = H, OMe, possess an unsaturated linkage between the chromophore and a nitrophenyl acceptor. While the parent chromophore [Pt(ttpy)(C triple-bond CC6H5)]PF6 is brightly luminescent in a fluid solution at 298 K, the triads exhibit complete quenching of the emission, as do the related donor-chromophore (D-C) dyads. Electrochemically, the triads and D-C dyads exhibit a quasi-reversible oxidation wave corresponding to the PTZ ligand, while the R = H triad and related C-A dyad display a facile quasi-reversible reduction assignable to the acceptor. TA spectroscopy shows that one of the triads possesses a long-lived charge-separated state of approximately 230 ns.

Synthesis, structure, characterization, and photophysical studies of a new platinum terpyridyl-based triad with covalently linked donor and acceptor groups.

A new terpyridyl-containing Pt triad [Pt(pytpy)(p-CC-C6H4-NH-CO-C6H2(OMe)3)](PF6)2 (4), where pytpy = 4'-(4-pyridin-1-ylmethylphenyl)-[2,2';6',2' ']terpyridine and p-CC-C6H4-NH-CO-C6H2(OMe)3 = N-(4-ethynylphenyl)-3,4,5-trimethoxybenzamide, has been synthesized and structurally characterized. The related donor-chromophore dyad [Pt(ttpy)(p-CC-C6H4-NH-CO-C6H2(OMe)3)]PF6 2, where ttpy = 4'-p-tolyl-[2,2';6',2' ']terpyridine, and the chromophore-acceptor dyad [Pt(pytpy)(CCC6H5)](PF6)2 (3), where CCC6H5 = ethynylbenzene, have also been studied. The multistep syntheses culminate with a CuI-catalyzed coupling reaction of the respective acetylene with either [Pt(ttpy)Cl]PF6 or [Pt(pytpy)Cl](PF6)2. X-ray and spectroscopic studies support assignment of a distorted square planar environment around the Pt(II) ion with three of its coordination sites occupied by the terpyridyl N-donors and the fourth coordination site occupied by the acetylenic carbon. Although the parent compound [Pt(ttpy)(CCC6H5)]PF6 (1) is brightly luminescent in fluid solution at 298 K, dyad 2 as well as triad 4 exhibit complete quenching of the emission. The chromophore-acceptor (C-A) dyad 3 displays weak solution luminescence at room temperature with a phi(rel)(em) of 0.011 (using Ru(bpy)3(2+) as a standard with phi(rel)(em) = 0.062). Electrochemically, the donor-chromophore (D-C) dyad and the donor-chromophore-acceptor (D-C-A) triad exhibit both metal-based and donor ligand-based oxidations, whereas the triad and the C-A dyad show the expected pyridinium- and terpyridine-based reductions. Transient absorption studies of the dyad and triad systems indicate that although the trimethoxybenzene group acts as a reductive donor, in the present system, the pyridinium group fails to act as an acceptor.

Facile synthesis, structure, and luminescence properties of Pt(diimine)bis(arylacetylide) chromophore-donor dyads.

The luminescent complex Pt(dpphen)bis(arylacetylide) complex (1) (dpphen = 4,7-diphenylphenanthroline and arylacetylide = 4-ethynylbenzaldehyde) has been synthesized and characterized structurally and spectroscopically. Complex 1 has been employed in the synthesis of donor-chromophore (D-C) dyads through Schiff base condensations of different anilines to give imine-linked dyads 2-4 and through imine reduction with borohydride, to give the corresponding amine-linked dyads 2a-4a. Crystal structure determinations of 1-4 and 4a establish a distorted square-planar geometry around the Pt(II) ion in each system with cis arylacetylide ligands and a diimine-constrained N-Pt-N bond angle of ca. 79.5 degrees. Complex 1 is strongly emissive having a relative quantum yield (phi) of 36% and an excited-state lifetime of 3.1 micros. In accord with the notion of photoinduced electron transfer from the aniline-based donor to the photoexcited chromophore, the emission of dyads 2-4 and 2a-4a is effectively quenched in all solvents tested. The intense absorption at 400 nm (30000-70000 L/mol.cm) for 2 and 2a has been assigned as an intraligand pi-pi* transition, whereas the lowest-energy transitions for all other dyads correspond to Pt-to-pi(diimine) MLCT transitions. Although the dyads can be synthesized in a facile manner, photolysis experiments reveal that both the imine and amine linkages are photochemically unstable, resulting in hydrolysis and regeneration of the aldehyde-containing chromophore 1.