Broad Variation Research Articles

CBCT-based online adaptive radiotherapy of the prostate bed: first clinical experience and comparison to nonadaptive conventional IGRT.

Conventional image-guided radiotherapy (IGRT) of the prostate bed is challenged by the varying anatomy due to dynamic changes of surrounding organs such as the bladder and rectum. This leads to changed dose coverage of target and surrounding tissue. The novel online adaptive radiotherapy (oART) aims to improve target coverage as well as reduce dose exposure to surrounding healthy tissues by daily reoptimization of treatment plans. Here we set out to quantify the resulting changes of this adaptation for patients and treatment team. Atotal of 198 fractions of radiotherapy of the prostate bed (6patients) were treated using oART with the Ethos accelerator (Varian Medical Systems, Palo Alto, CA, USA). For each fraction, volumes and several dose-volume parameters of target volumes and organs at risk were recorded for the scheduled plan (initial plan, recalculated based on daily cone beam computed tomography [CBCT]), the adapted plan, and the verification plan, which is the dose distribution of the applied plan recalculated on the closing CBCT after the adaptation process. Clinical acceptability for all plans was determined using given dose-volume parameters of target volumes. Additionally, the time needed for the adaptation process was registered and compared to the time required for the daily treatment of five conventional IGRT patients. Volumes of target and organs at risk (OAR) exhibited broad variation from day to day. The differences in dose coverage D98% of the clinical target volume (CTV) were significant through adaptation (p < 0.0001; median D98% 97.1-98.0%) and further after verification CBCT (p < 0.001; median D98% 98.1%). Similarly, differences in D98% of the planning target volume (PTV) were significant with adaptation (p < 0.0001; median D98% 91.8-96.5%) and after verification CBCT (p < 0.001; median D98% 96.4%) with decreasing interquartile ranges (IQR). Dose to OAR varied extensively and did not show aconsistent benefit from oART but decreased in IQR. Clinical acceptability increased significantly from 19.2% for scheduled plans to 76.8% for adapted plans and decreased to 70.7% for verification plans. The scheduled plan was never chosen for treatment. The median time needed for oART was 25 min compared to 8 min for IGRT. Target dose coverage was significantly improved using oART. IQR decreased for target coverage as well as OAR doses indicating higher repeatability of dose delivery using oART. Differences in doses after verification CBCT for targets as well as OAR were significant compared to adapted plans but did not offset the overall dosimetric gain of oART. The median time required is three times higher for oART compared to IGRT.

Intraspecific diversity is critical to population-level risk assessments

Environmental risk assessment (ERA) is critical for protecting life by predicting population responses to contaminants. However, routine toxicity testing often examines only one genotype from surrogate species, potentially leading to inaccurate risk assessments, as natural populations typically consist of genetically diverse individuals. To evaluate the importance of intraspecific variation in translating toxicity testing to natural populations, we quantified the magnitude of phenotypic variation between 20 Daphnia magna clones exposed to two levels of microcystins, a cosmopolitan cyanobacterial toxin. We observed significant genetic variation in survival, growth, and reproduction, which increased under microcystins exposure. Simulations of survival showed that using a single genotype for toxicity tolerance estimates on average failed to produce accurate predictions within the 95% confidence interval over half of the time. Whole genome sequencing of the 20 clones tested for correlations between toxicological responses and genomic divergence, including candidate loci from prior gene expression studies. We found no overall correlations, indicating that clonal variation, rather than variation at candidate genes, predicts population-level responses to toxins. These results highlight the importance of incorporating broad intraspecific genetic variation, without focusing specifically on variation in candidate genes, into ERAs to more reliably predict how local populations will respond to contaminants.

Engineering quantitative stomatal trait variation and local adaptation potential by cis-regulatory editing.

Cis-regulatory element editing can generate quantitative trait variation that mitigates extreme phenotypes and harmful pleiotropy associated with coding sequence mutations. Here, we applied a multiplexed CRISPR/Cas9 approach, informed by bioinformatic datasets, to generate genotypic variation in the promoter of OsSTOMAGEN, a positive regulator of rice stomatal density. Engineered genotypic variation corresponded to broad and continuous variation in stomatal density, ranging from 70% to 120% of wild-type stomatal density. This panel of stomatal variants was leveraged in physiological assays to establish discrete relationships between stomatal morphological variation and stomatal conductance, carbon assimilation and intrinsic water use efficiency in steady-state and fluctuating light conditions. Additionally, promoter alleles were subjected to vegetative drought regimes to assay the effects of the edited alleles on developmental response to drought. Notably, the capacity for drought-responsive stomatal density reprogramming in stomagen and two cis-regulatory edited alleles was reduced. Collectively our data demonstrate that cis-regulatory element editing can generate near-isogenic trait variation that can be leveraged for establishing relationships between anatomy and physiology, providing a basis for optimizing traits across diverse environments.

Polyphenolic Profile and Antioxidant Activity of Whole Grape Juices from Vitis labrusca and Brazilian Hybrid Grapes in Two Training Systems.

The phenolic profile and antioxidant activity of whole grape juices from Vitis labrusca and Brazilian hybrids in two training systems were analyzed. Genotypes of V. labrusca ('Bordô' and 'Isabel') and Brazilian hybrids ('IAC 138-22 Máximo' and 'BRS Violeta') were grafted onto the rootstock 'IAC 766 Campinas' (106-8 'Mgt' × Vitis caribaea) and trained on low and high trellis. After harvest, the grapes were destemmed and the berries macerated in a roller crusher. Following hot extraction without pressurization of the pomace and gentle pressing of the blend (skins, must, and seeds), the juices were bottled in amber glass bottles and pasteurized. The physicochemical and colorimetric parameters of the juices, as well as the levels of flavonoids, phenolic compounds, total monomeric anthocyanins, antioxidant activity, and polyphenolic profile, were evaluated. The juices were also subjected to sensory analysis (CAAE: 65549817.7.0000.5411). There was broad variation in all assessed characteristics. The results obtained demonstrate that the training system and grape genotype used in juice production are highly related to the presence of sugars, acidity, and bioactive compounds. Juices made from 'Bordô', 'IAC 138-22 Máximo' and 'BRS Violeta' grapes stood out from 'Isabel' juices, the main grape variety used in Brazilian juice and wine production. All juices contain bioactive compounds in considerable concentrations, indicating beverages with high antioxidant activity and, consequently, high biological potential, with the use of high trellis in vine cultivation potentially increasing concentrations.

Trading in the Quantum Era: optimizing Bitcoin gains and energy costs

ABSTRACT This paper presents an in-depth analysis of a Quantum-inspired Multi-objective Optimization Algorithm (QMOA) applied to a unique problem: maximizing trading profits while minimizing energy costs. Previous investigations have explored the profitability of Bitcoin, yet our research delves into its relationship with energy costs. Regarding the trade-offs, the Pareto analysis reveals that trading profit and energy cost do not strongly inversely correlate. The range of outcomes shows a relatively uniform trading profit (from 1.302,85 to 1.310,22$), but a broader variation in energy costs (from 1.141,66 to 5.657,94$). While the trading profit remains stable, there is a wide array of options for minimizing energy cost, which is influenced by various constraints and market conditions. Solutions tend to cluster more in areas of higher energy costs. However, the variability in energy costs offers Bitcoin miners choices, allowing them to tailor strategies, whether that involves prioritizing energy efficiency, profit maximization or striking a balance.

Regulatory logic and transposable element dynamics in nematode worm genomes.

Genome sequencing has revealed a tremendous diversity of transposable elements (TEs) in eukaryotes but there is little understanding of the evolutionary processes responsible for TE diversity. Non-autonomous TEs have lost the machinery necessary for transposition and rely on closely related autonomous TEs for critical proteins. We studied two mathematical models of TE regulation, one assuming that both autonomous tranposons and their non-autonomous relatives operate under the same regulatory logic, competing for transposition resources, and one assuming that autonomous TEs self-attenuate transposition while non-autonomous transposons continually increase, parasitizing their autonomous relatives. We implemented these models in stochastic simulations and studied how TE regulatory relationships influence transposons and populations. We found that only outcrossing populations evolving with Parasitic TE regulation resulted in stable maintenance of TEs. We tested our model predictions in Caenorhabditis genomes by annotating TEs in two focal families, autonomous LINEs and their non-autonomous SINE relatives and the DNA transposon Mutator . We found broad variation in autonomous - non-autonomous relationships and rapid mutational decay in the sequences that allow non-autonomous TEs to transpose. Together, our results suggest that individual TE families evolve according to disparate regulatory rules that are relevant in the early, acute stages of TE invasion.

Broad geographic variation in age- and sex-dependent origin of harvested eurasian wigeon (Mareca penelope) revealed by stable-hydrogen (δ2H) isotope analyses of feathers

Migratory waterfowl are a harvested resource shared among multiple European countries, exposing them to potential overexploitation. Management of take is challenging since the life cycle of migratory waterfowl consists of several stages distributed among several locations, with possible spatio-temporal overlap among populations with differing population trends. Successful harvest management in such situations requires knowledge about the connections between breeding and non-breeding locations, and where birds are harvested. Breeding populations of Eurasian wigeon (Mareca penelope) are declining in Finland, underlining the need for more effective harvest management. Relative proportions and temporal distribution of local breeding birds and migrants from a larger Russian breeding population within the Finnish hunting bag has been unknown to date. We studied spatio-temporal origins of Finnish harvested wigeon by measuring stable-hydrogen (δ2H) isotope values from legally harvested birds. We modelled the changes in δ2H values of the feather samples within the hunting season using Gaussian processes and found that the origin of harvested wigeon in Finland changed during the hunting season and differed by age and sex. In juveniles and adult females but not in adult males, origin of harvested birds shifted from local and possibly western Russian birds to more long-distance migratory birds during the harvest season. These patterns likely reflected sex- and age-specific differences in migratory behaviour of Eurasian wigeon in the East Atlantic flyway, which can be used to guide future management and conservation of this species through the implementation of spatio-temporal harvest regulation.

In-depth analysis of Bt cotton adoption: farmers' opinions, genetic landscape, and varied perspectives—a case study from Pakistan

BackgroundBt technology has played significant role in controlling bollworms and increasing cotton yield in earlier days of its introduction, a subsequent decline in yield became apparent over time. This decline may be attributed to various environmental factors, pest dynamics, or combination of both. Therefore, the present biophysical survey and questionnaire were designed to evaluate the impact of Bt cotton on bollworms management and its effect on reducing spray costs, targeting farmers with varied landholdings and educational backgrounds. Additionally, data on farmers' cultivated varieties and the prevalence of bollworms and sucking insects in their fields were recorded. Subsequently, about eleven thousand cotton samples from farmer fields were tested for Cry1Ac, Cry2Ab and Vip3A genes by strip test.ResultsIn this analysis, 83% of the farmers planting approved varieties believe that Bt technology control bollworms, while 17% hold contradictory views. Similarly, among farmers cultivating unapproved varieties, 77% agree on effectiveness of Bt technology against bollworms, while 23% disagree. On the other hand, 67% of farmers planting approved varieties believe that Bt technology does not reduce spray costs, while 33% agree with the effectiveness. Similarly, 78% of farmers cultivating unapproved varieties express doubt regarding its role to reduce spray costs, while 22% are in favour of this notion. Differences in opinions on the effectiveness of Bt cotton in controlling bollworms and reducing spray cost between farmers planting unapproved and approved varieties may stem from several factors. One major cause is the heavy infestation of sucking insects, which is probably due to the narrow genetic variation of the cultivated varieties. Additionally, the widespread cultivation of unapproved varieties (21.67%) is also an important factor to cause different opinions on the effectiveness of Bt cotton.ConclusionBased on our findings, we propose that the ineffective control of pests on cotton crop may be attributed to large scale cultivation of unapproved varieties and non-inclusion of double and triple transgene technologies in country’s sowing plan. On the basis of our findings, we suggest cotton breeders, regulatory bodies and legislative bodies to discourage the cultivation of unapproved varieties and impure seed. Moreover, the adoption of double and triple Bt genes in cottons with a broad genetic variation could facilitate the revival of the cotton industry, and presenting a promising way forward.

Prediction on the chin advancement of the twin block functional appliance in growing Chinese patients using the cephalometric markers: a retrospective study.

In spite of the widespread use of functional appliances, broad variations were applied the treatment response. The aim of this study is to investigate the pre-treatment cephalometric predictors on the chin advancement of twin-block in growing Chinese patients with class II malocclusion. After screening, 90 patients treated by twin-block were included in the study. The treatment outcome was assessed by the alterations in the distance of skeletal pogonion (Pog) to the vertical reference plane perpendicular to the Frankfurt plane (ΔPog-VRP). Moreover, ΔPog-VRP was divided by the cranial growth indicated by the Nasion to Basion changes (ΔN-Ba) to minimize the growth discrepancy among individuals (adjΔPog-VRP). Patients with ΔPog-VRP/adjΔPog-VRP above the median value were categorized into good response group (GRG/adjGRG, N = 45), while the rest were poor response group (PRG/adjPRG, N = 45). Independent t-test was used to compare the pre-treatment cephalometric measurements between GRG/adjGRG and PRG/adjPRG. Stepwise multivariate regression models were used to determine the pre-treatment cephalometric predictors for the chin advancement. Generally, there were not any significant differences between GRG/adjGRG and PRG/adjPRG regarding age, gender and cervical stage before twin-block treatment. Patients from GRG had significantly reduced cephalometric measurements in the vertical dimensions, including ∠N-Go-Me, ∠Mandibular plane-Occlusal plane (∠MP-OP) and the sum of angles (p < 0.05) in comparison to PRG. When the individual growth was taken account, similar findings were observed. The patients from adjGRG had a significantly lower ∠Sella Nasion line-MP (∠SN-MP), ∠Ar-Go-Me and ∠N-Go-Me, as well as an increased Posterior facial height (PFH)/Anterior facial height (AFH) (p < 0.05) compared with their counterparts. ∠N-Go-Me variable was the independent predictor on Pog advancement with (β = -0.26, 95% CI: -0.06 to -0.01, p = 0.01) and without (β = -0.29, 95% CI: -0.06 to -0.01, p < 0.01) adjustments on individual growth. The results of this study showed that patients with a reduced N-Go-Me angle are more likely to experience a greater chin advancement following twin-block treatment.

Commercially available carrageenans show broad variation in their structure, composition, and functionality

Carrageenans are polysaccharides from red algae which are widely used as food additives and in other applications. Their structure is often described by different disaccharide repeating units, although it was already demonstrated that reality is more complex. In many studies, commercial carrageenans were used to establish structure function relationships, but a structural and compositional analysis was rarely conducted. Therefore, the aim of our study was to systematically and comprehensively characterize a broad collection of commercial carrageenans with different specifications from different manufacturers. For a more detailed characterization, an analytical approach based on partial enzymatic hydrolysis in combination with HPLC–MS and HPSEC-RI was developed and applied. Furthermore, rheology was used to gain detailed insights into the functionality of selected samples. Our results demonstrate that significant structural variation can be observed for commercial carrageenans. The samples contained different cations and the carrageenan type specified by the manufacturer did not always represent the structure of the corresponding polysaccharides. This was especially true for λ-carrageenans: Of the six commercial samples analyzed, none contained structural elements from the λ-type. Instead, the corresponding carrageenans contained κ-, ι- and ν-units. The application of the developed enzymatic-chromatographic approach showed that different hybrid carrageenans are present. In addition, the rheological analysis of the commercial carrageenan samples showed clear differences in the gelling properties upon calcium addition which could influence their behavior in different applications. Our results demonstrate that before an investigation of structure–function relationships, commercial carrageenan samples should be analyzed for their structure and composition. We also showed that the enzymatic-chromatographic approach described in this study is well suited for this purpose.

Nonpeptidic Irreversible Inhibitors of SARS-CoV-2 Main Protease with Potent Antiviral Activity.

SARS-CoV-2 infections pose a high risk for vulnerable patients. In this study, we designed benzoic acid halopyridyl esters bearing a variety of substituents as irreversible inhibitors of the main viral protease (Mpro). Altogether, 55 benzoyl chloro/bromo-pyridyl esters were synthesized, with broad variation of the substitution pattern on the benzoyl moiety. A workflow was employed for multiparametric optimization, including Mpro inhibition assays of SARS-CoV-2 and related pathogenic coronaviruses, the duration of enzyme inhibition, the compounds' stability versus glutathione, cytotoxicity, and antiviral activity. Several compounds showed IC50 values in the low nanomolar range, kinact/Ki values of >100,000 M-1 s-1 and high antiviral activity. High-resolution X-ray cocrystal structures indicated an important role of ortho-fluorobenzoyl substitution, forming a water network that stabilizes the inhibitor-bound enzyme. The most potent antiviral compound was the p-ethoxy-o-fluorobenzoyl chloropyridyl ester (PSB-21110, 29b, MW 296 g/mol; EC50 2.68 nM), which may serve as a lead structure for broad-spectrum anticoronaviral therapeutics.

Genetic parameters of yield component and yield in M1 rice (Oryza sativa L.) generation irradiated with gamma-ray

High-yielding varieties are the primary determinant of the success of increasing Indonesia's rice production. Plant breeding for new high-yielding varieties is possible through mutation induction and selecting desired traits. The effectiveness and efficiency of selection require comprehensive genetic parameters. This study aimed to study the genetic diversity, heritability, genetic advance, and relationship between yield components and yield in the M1 generation of mutant rice irradiated with gamma ray. This research used a factorial randomized complete block design, involving gamma irradiation doses of 100 Gy, 150 Gy, and 200 Gy, as the first factor; and the second factor was the rice genotype: UnsoedBDBP, UnsoedBDIU, UnsoedBPIU, UnsoedIUBD, and UnsoedIBP. Each treatment was repeated three times. Results showed that traits with broad genetic variation were tiller number plant-1, grain number panicle-1, and grain yield plant-1. High heritability and genetic advance values were found in plant height, grain number panicle-1, and yield plant-1, indicating that improvement in these traits can be achieved simply through selection methods. Panicle number plant-1 and filled grain percentage panicle-1 showed a unidirectional relationship and directly affected high values on yield plant-1. Therefore, these traits can be considered selection indicators for breeding high-yielding mutant rice.

Genetic Diversity and Population Structural Analysis Reveal the Unique Genetic Composition of Populus tomentosa Elite Trees

Genetic diversity analysis provides the scientific basis for the preservation, evaluation, and utilization of the germplasm resources of tree species. We explored the genetic diversity and structure of Populus tomentosa elite trees in North China using 13 nuclear microsatellite markers. We compared nine groups of accessions including 20 originating from Beijing (BJ), 122 from Hebei (HB), 20 from Shandong (SD), 113 from Henan (HN), 270 from Shanxi (SX), 54 from Shaanxi (SAX), 8 from Gansu (GS), 10 from Anhui (AH), and 6 from Jiangsu (JS). All of the studied primer pairs were polymorphic and generated 125 alleles. Analyses of molecular variance revealed that 79%, 14%, and 8% of the total variation was due to variations within the individual, among individuals, and among populations, respectively. Based on principal coordinate and STRUCTURE cluster analyses, individuals distributed in the southern region (HN, SAX, AH, and JS) were roughly classified into one group, while those distributed in the northeastern region (BJ, HB, and SD) and northwestern regions (SX) were separately divided into one group each. Moreover, the northwestern region included two-thirds of the SX trees, and the remainder were in the northeast region. By analyzing genetic diversity and structure within populations, individuals with different genetic backgrounds were screened for constituent training populations (TRS), including broad allelic variation for related traits. This ensures that the genomic prediction model can accurately capture genetic effects and provide reliable predictions across a broad spectrum of genetic backgrounds. Therefore, our results will benefit genome breeding technology.

Functionalizing Thiosemicarbazones for Covalent Conjugation.

Thiosemicarbazones (TSCs) with their modular character (thiosemicarbazides + carbonyl compound) allow broad variation of up to four substituents on the main R1R2C=N(1)-NH-C(S)-N(4)R3R4 core and are thus interesting tools for the formation of conjugates or the functionalization of nanoparticles (NPs). In this work, di-2-pyridyl ketone was introduced for the coordination of metals and 9-anthraldehyde for luminescence as R1 and R2 to TSCs. R3 and R4 substituents were varied for the formation of conjugates. Amino acids were introduced at the N4 position to produce [R1R2TSC-spacer-amino acid] conjugates. Further, functions such as phosphonic acid (R-P(O)(OH)2), D-glucose, o-hydroquinone, OH, and thiol (SH) were introduced at the N4 position producing [R1R2TSC-spacer-anchor group] conjugates for direct NP anchoring. Phenyl, cyclohexyl, benzyl, ethyl and methyl were used as spacer units. Both phenyl phosphonic acid TSC derivatives were bound on TiO2 NPs as a first example of direct NP anchoring. [R1R2TSC-spacer-end group] conjugates including OH, S-Bn (Bn = benzyl), NH-Boc (Boc = tert-butyloxycarbonyl), COOtBu, C≡CH, or N3 end groups were synthesized for potential covalent binding to functional molecules or functionalized NPs through amide, ester, or triazole functions. The synthesis of the thiosemicarbazides H2NNH-C(S)-NR3R4 starting from amines, including amino acids, SCCl2 or CS2, and hydrazine and their condensation with dipyridyl ketone and anthraldehyde led to 34 new TSC derivatives. They were synthesized in up to six steps with overall yields ranging from 10 to 85% and were characterized by a combination of nuclear magnetic resonance spectroscopy and mass spectrometry. UV-vis absorption and photoluminescence spectroscopy allowed us to easily trace the dipyridyl imine and anthracene chromophores.

Prion protein gene (PRNP) variation in German and Danish cervids

The structure of cellular prion proteins encoded by the prion protein gene (PRNP) impacts susceptibility to transmissible spongiform encephalopathies, including chronic wasting disease (CWD) in deer. The recent emergence of CWD in Northern European reindeer (Rangifer tarandus), moose (Alces alces alces) and red deer (Cervus elaphus), in parallel with the outbreak in North America, gives reason to investigate PRNP variation in European deer, to implement risk assessments and adjust CWD management for deer populations under threat. We here report PRNP-sequence data from 911 samples of German red, roe (Capreolus capreolus), sika (Cervus nippon) and fallow deer (Dama dama) as well as additional data from 26 Danish red deer close to the German border and four zoo species not native to Germany. No PRNP sequence variation was observed in roe and fallow deer, as previously described for populations across Europe. In contrast, a broad PRNP variation was detected in red deer, with non-synonymous polymorphisms at codons 98, 226 and 247 as well as synonymous mutations at codons 21, 78, 136 and 185. Moreover, a novel 24 bp deletion within the octapeptide repeat was detected. In summary, 14 genotypes were seen in red deer with significant differences in their geographical distribution and frequencies, including geographical clustering of certain genotypes, suggesting “PRNP-linages” in this species. Based on data from North American CWD and the genotyping results of the European CWD cases, we would predict that large proportions of wild cervids in Europe might be susceptible to CWD once introduced to naive populations.

Resistive switching suppression in metal/Nb:SrTiO3 Schottky contacts prepared by room-temperature pulsed laser deposition

Deepening the understanding of interface-type resistive switching (RS) in metal/oxide heterojunctions is a key step for the development of high-performance memristors and Schottky rectifiers. In this study, we address the role of metallization technique by fabricating prototypical metal/Nb-doped SrTiO3 (M/NSTO) Schottky contacts via pulsed laser deposition (PLD). Ultrathin Pt and Au electrodes are deposited by PLD onto single-crystal (001)-terminated NSTO substrates and interfacial transport is characterized by conventional macroscale methods and nanoscale Ballistic Electron Emission Microscopy. We show that PLD metallization gives Schottky contacts with highly reversible current-voltage characteristics under cyclic polarization. Room-temperature (RT) transport is governed by thermionic emission with Schottky barrier height ϕB(Pt/NSTO)∼0.71−0.75eV , ϕB(Au/NSTO)∼0.70−0.83eV and ideality factors as small as n(Pt/NSTO)∼1.1 and n(Au/NSTO)∼1.6 . RS remains almost completely suppressed upon imposing broad variations of the Nb doping and of the external stimuli (polarization bias, working temperature, ambient air exposure). At the nanoscale, we find that both systems display high spatial homogeneity of ϕB ( ⩽50meV ), which is only partially affected by the NSTO mixed termination ( |ϕB(M/SrO)−ϕB(M/TiO2)|<35meV ). Experimental evidences and theoretical arguments—based on a metal-insulator-semiconductor description of the M/NSTO—indicate that the PLD metallization mitigates interfacial layer effects responsible for RS. This occurs thanks to the reduction of the interfacial layer thickness and to the creation of an effective barrier against the permeation of ambient gas species affecting charge trapping and redox reactions. This description allows to rationalize interfacial aging effects, observed upon several-months-exposure to ambient air, in terms of a slow interfacial re-oxidation. Our work contributes to the fundamental understanding of interface-type RS and demonstrates that RT PLD offers a viable platform for the realization of robust, RS-free NSTO-based Schottky contacts.

Genetic variability, association and diversity analysis of yield and its component traits in rice (Oryza sativa) germplasm

An experiment was conducted during winter (rabi) season of 2022 at ICAR-Indian Institute of Rice Research, Hyderabad, Telangana to evaluate extent of genetic variability, heritability, diversity and the relationship between yield and its component traits in a collection of 60 rice germplasm accessions. Results showed that germplasm accessions exhibited ample genetic variability and diversity for yield traits. Based on per se performance, inter crosses between the genotypes IC458483 with high grain yield, IC210775 with more panicle length, IC75919 with high 100-grain weight, IC75980 with more productive tillers and IC75965 with high protein content could produce positive transgressive segregants for improving respective traits. Plant height, total and effective tillers, grain yield and 100-grain weight traits which exhibited the highest heritability and genetic advance could be vital for selection in hybridization programmes. Crossing among genotypes of diverse clusters specifically VI, VII and VIII is suggested as this could create a broad variation useful for selecting genotypes with both high yield and long panicles.

Variation in pollen viability among Leptochloa crinita accessions: implications for directed crosses

ABSTRACT Leptochloa crinita, a native forage grass from American arid regions, is widely used for range grazing and revegetation of degraded lands. Despite its importance, progress in breeding and genetic research has been hindered by the difficulty of achieving sexual crosses between L. crinita plants. We hypothesize that factors associated with pollen quality can influence the effectiveness of directed sexual crosses in this species. Thus, the present study investigated pollen viability and longevity in a genetically diverse collection of 21 L. crinita accessions. Pollen viability was estimated at 0, 30, 60, and 180 minutes after anthers dehiscence (MAAD) by two methods: 1) acetocarmine staining; and 2) in vitro germination of pollen grains in culture media containing 0.4-1.0 M sucrose. The staining method overestimated pollen viability, whereas the in vitro germination assay provided accurate and reliable estimates, being 0.6 M the optimal sucrose concentration in the medium, in terms of germination rates and discriminatory power among the accessions. In all the accessions, pollen viability was highest at 0-30 MAAD, and decayed very rapidly, to reach levels below 5% at 180 MAAD. Significant (p<0.05) and broad variation for pollen viability was found among the accessions, with mean values in the range of 49-89% (0 MAAD), 32-76% (30 MAAD), 24-45% (60 MAAD), and 0.6-4.9% (180 MAAD), allowing the identification of six accessions exhibiting the greatest pollen viabilities. These results suggest 0-30 MAAD and using the selected (best) pollen donors, on emasculated female parentals, as the optimal conditions for attempting sexual crosses in L. crinita.

Blood Flow Restriction Therapy After Anterior Cruciate Ligament Reconstruction

Anterior cruciate ligament reconstruction (ACLR) rehabilitation necessitates restoration of quadriceps strength to minimize reinjury and optimize return to sport (RTS). Patients recovering from ACLR are limited by pain and activity restrictions, resulting in quadriceps muscle atrophy. Blood flow restriction (BFR) therapy involves performing exercises while a specialized blood pressure cuff is applied to the proximal aspect of the operative extremity and inflated to 40% to 90% of the arterial occlusion pressure, as determined using Doppler ultrasonography. BFR is theorized to induce an anaerobic environment and metabolic stress during exercise, promoting muscle hypertrophy and strength gains. Although the physiological mechanism has not been fully elucidated, it is theorized that BFR combined with low-load resistance training could yield muscle adaptations comparable to those of high-load resistance training. For ACLR patients with pain and restrictions precluding high-intensity strength training, incorporation of BFR into postoperative rehabilitation protocols could help mitigate quadriceps weakness and promote RTS. Randomized controlled trials report a prolonged, dose-dependent relation between BFR use and quadriceps and hamstring strength gains, improved bone and muscle mass, and earlier RTS, whereas other studies report no significant difference in quadriceps size, strength, or patient satisfaction compared with controls. Furthermore, although generally considered safe, there are rare reports of associated adverse events such as rhabdomyolysis, and BFR should be avoided in patients with a history of thromboembolic disease or peripheral vasculopathy. The literature examining BFR after ACLR is heterogeneous; lacks standardization; and contains broad variation in reported cuff pressures, as well as timing and duration of BFR use, among protocols. Although the use of BFR after ACLR shows promise, further study is necessary to elucidate the efficacy, safety, and optimal protocols.

High-throughput fitness experiments reveal specific vulnerabilities of human-adapted Salmonella during stress and infection

Salmonella enterica is comprised of genetically distinct ‘serovars’ that together provide an intriguing model for exploring the genetic basis of pathogen evolution. Although the genomes of numerous Salmonella isolates with broad variations in host range and human disease manifestations have been sequenced, the functional links between genetic and phenotypic differences among these serovars remain poorly understood. Here, we conduct high-throughput functional genomics on both generalist (Typhimurium) and human-restricted (Typhi and Paratyphi A) Salmonella at unprecedented scale in the study of this enteric pathogen. Using a comprehensive systems biology approach, we identify gene networks with serovar-specific fitness effects across 25 host-associated stresses encountered at key stages of human infection. By experimentally perturbing these networks, we characterize previously undescribed pseudogenes in human-adapted Salmonella. Overall, this work highlights specific vulnerabilities encoded within human-restricted Salmonella that are linked to the degradation of their genomes, shedding light into the evolution of this enteric pathogen.