Genome sequencing and assembly of Indian golden silkmoth, Antheraea assamensis Helfer (Saturniidae, Lepidoptera).

Muga silkworm (Antheraea assamensis), one of the economically important wild silkmoths, is unique among saturniid silkmoths. It is confined to the North-eastern part of India. Muga silk has the highest value among the other silks. Unlike other silkmoths, A. assamensis has a low chromosome number (n = 15), and ZZ/ZO sex chromosome system. Here, we report the first high-quality draft genome of A. assamensis, assembled by employing the Illumina and PacBio sequencing platforms. The assembled genome of A. assamensis is 501.18 Mb long, with 2697 scaffolds and an N50 of 683.23 Kb. The genome encompasses 18,385 protein-coding genes, 86.29% of which were functionally annotated. Phylogenetic analysis of A. assamensis revealed its divergence from other Antheraea species approximately 28.7 million years ago. Moreover, an investigation into detoxification-related gene families, CYP450, GST, and ABC-transporter, revealed a significant expansion in A. assamensis as compared to the Bombyx mori. This expansion is comparable to Spodoptera litura, suggesting adaptive responses linked to the polyphagous behavior observed in these insects. This study provides valuable insights into the molecular basis of evolutionary divergence and adaptations in muga silkmoth. The genome assembly reported in this study will significantly help in the functional genomics studies on A. assamensis and other Antheraea species along with comparative genomics analyses of Bombycoidea insects.

Computational approaches for identifying disease-causing mutations in proteins.

Advancements in genome sequencing have expanded the scope of investigating mutations in proteins across different diseases. Amino acid mutations in a protein alter its structure, stability and function and some of them lead to diseases. Identification of disease-causing mutations is a challenging task and it will be helpful for designing therapeutic strategies. Hence, mutation data available in the literature have been curated and stored in several databases, which have been effectively utilized for developing computational methods to identify deleterious mutations (drivers), using sequence and structure-based properties of proteins. In this chapter, we describe the contents of specific databases that have information on disease-causing and neutral mutations followed by sequence and structure-based properties. Further, characteristic features of disease-causing mutations will be discussed along with computational methods for identifying cancer hotspot residues and disease-causing mutations in proteins.

Brain health measurement: a scoping review.

OBJECTIVES: Preservation of brain health is an urgent priority for the world's ageing population. The evidence base for brain health optimisation strategies is rapidly expanding, but clear recommendations have been limited by heterogeneity in measurement of brain health outcomes. We performed a scoping review to systematically evaluate brain health measurement in the scientific literature to date, informing development of a core outcome set. DESIGN: Scoping review. DATA SOURCES: Medline, APA PsycArticles and Embase were searched through until 25 January 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they described brain health evaluation methods in sufficient detail in human adults and were in English language. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened titles, abstracts and full texts for inclusion and extracted data using Covidence software. RESULTS: From 6987 articles identified by the search, 727 studies met inclusion criteria. Study publication increased by 22 times in the last decade. Cohort study was the most common study design (n=609, 84%). 479 unique methods of measuring brain health were identified, comprising imaging, cognitive, mental health, biological and clinical categories. Seven of the top 10 most frequently used brain health measurement methods were imaging based, including structural imaging of grey matter and hippocampal volumes and white matter hyperintensities. Cognitive tests such as the trail making test accounted for 286 (59.7%) of all brain health measurement methods. CONCLUSIONS: The scientific literature surrounding brain health has increased exponentially, yet measurement methods are highly heterogeneous across studies which may explain the lack of clinical translation. Future studies should aim to develop a selected group of measures that should be included in all brain health studies to aid interstudy comparison (core outcome set), and broaden from the current focus on neuroimaging outcomes to include a range of outcomes.

Insights into the genotype-phenotype relationship of ocular manifestations in Kabuki syndrome.

We aim to assess if genotype-phenotype correlations are present within ocular manifestations of Kabuki syndrome (KS) among a large multicenter cohort. We conducted a retrospective, medical record review including clinical history and comprehensive ophthalmological examinations of a total of 47 individuals with molecularly confirmed KS and ocular manifestations at Boston Children's Hospital and Cincinnati Children's Hospital Medical Center. We assessed information regarding ocular structural, functional, and adnexal elements as well as pertinent associated phenotypic features associated with KS. For both type 1 KS (KS1) and type 2 KS (KS2), we observed more severe eye pathology in nonsense variants towards the C-terminus of each gene, KMT2D and KDM6A, respectively. Furthermore, frameshift variants appeared to be not associated with structural ocular elements. Between both types of KS, ocular structural elements were more frequently identified in KS1 compared with KS2, which only involved the optic disc in our cohort. These results reinforce the need for a comprehensive ophthalmologic exam upon diagnosis of KS and regular follow-up exams. The specific genotype may allow risk stratification of the severity of the ophthalmologic manifestation. However, additional studies involving larger cohorts are needed to replicate our observations and conduct powered analyses to more formally risk-stratify based on genotype, highlighting the importance of multicenter collaborations in rare disease research.

Fungal Endophytes: A Storehouse of Bioactive Compounds.

Fungal endophytes are the microbial adaptations that usually enter the plant tissues during their life cycle without harming the host plants. They are found everywhere on earth and generally depend on the hosts by developing various symbiotic relationships, like mutualism, hostility, and parasitism on rare occasions, leading to the growth and rise in the nutrient content of the hosts. Endophytes can develop tolerance in host organisms against the stresses induced by either living or non-living agents. They may protect them from insects or pests by building resistance. Interestingly, endophytes can synthesize many phytohormones, natural medicinal compounds and several essential enzymes beneficial for biotechnological perspectives that can be obtained by culturing plant tissue in a suitable medium. These endophytes are a reservoir of many new active phytoconstituents, like alkaloids, phenolics, steroids, quinones, tannins, saponins, etc., which exhibit anticancer, antiinsecticidal, antioxidant, antibacterial, antiviral, antifungal, and many more properties. Exploring the new bioactive chemical entities from the endophytes may supply potent lead compounds for drug discovery to combat numerous disease conditions. Hence, the present review was carried out to explore the significance of the fungal endophytes and their medicinal, food, and cosmetic use.

Drought index predictability for historical and future periods across the Southern plain of Nepal Himalaya.

Drought episodes across the Himalayas are inevitable due to rapidly increasing atmospheric temperatures and uncertainties in rainfall patterns. Tarai of Nepal is a tropical region located in the foothills of the Central Himalaya as a country's food granary with a contribution of over 50% to the entire country's agricultural production. However, there is a lack of detailed studies exploring the spatiotemporal occurrence of drought in these regions under the changing climate. In this study, we used the ensemble of nine climate models from the Coupled Model Intercomparison Project Phase 6 (CMIP6) under two shared socio-economic pathways (SSPs), namely SSP245 (an intermediate development pathway) and SSP585 (a high development pathway), to assess anticipated drought during the mid-century. We used bias-corrected gridded data from the Worldclim to project drought events by the end of the mid-century based on the historical period (1989-2018). We computed historical and projected Thornthwaite moisture index (TMI) to evaluate soil moisture conditions on a seasonal scale for the Tarai region's Eastern, Central, and Western parts. The model ensemble projected a significant increase in precipitation and temperature for the entire Tarai by the end of mid-century. However, the winter and spring seasons are projected to suffer precipitation deficiency and a temperature rise. Our results indicated that the Eastern Tarai would likely experience a decrease in winter precipitation. We emphasize that the presented spatiotemporal pattern of the MI will be instrumental in addressing the irrigation facility's needs, choice, and rotation of crops under the changing climate scenarios and in improving our mitigation measures and adaptation plans for sustainability of the agriculture in drought-prone areas.

Pyridine: the scaffolds with significant clinical diversity.

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research. This privileged scaffold has been consistently incorporated in a diverse range of drug candidates approved by the FDA (Food and Drug Administration). This moiety has attracted increasing attention from several disease states owing to its ease of parallelization and testing potential pertaining to the chemical space. In the next few years, a larger share of novel pyridine-based drug candidates is expected. This review unifies the current advances in novel pyridine-based molecular frameworks and their unique clinical relevance as reported over the last two decades. It highlights an inclination to the use of pyridine-based molecules in drug crafting and the subsequent emergence of several potent and eligible candidates against a range of diversified diseases.

An Innovative Case Management and Immigrant Onboarding Model Developed by the Sharewood Project in Massachu.

The Sharewood Project, a student-run free project developed by Tufts University School of Medicine students in 1997, provides limited medical care and social services to a diverse population in Malden, Massachusetts. The project plays an unusual role in introducing immigrants to the health care and education systems in Massachusetts.

Congenital microgastria-limb reduction association: A case report and review of the literature.

We report a patient with phenotypic semblance to the congenital microgastria-limb reduction association (MLRD). Our patient presented with microgastria, bilateral upper limb anomalies, asplenia, solitary kidney, and mild micrognathia. In addition to the anomalies seen in our patient, MLRD has been associated with respiratory, cardiovascular, and central nervous system anomalies. MLRD is thought to arise from a developmental field defect during embryonic weeks five and six; however, no genetic cause has been elucidated. Along with our patient presentation, we review the literature to further our understanding of the MLRD phenotype spectrum.

Copper-Catalyzed Thiolation of Terminal Alkynes Employing Thiocyanate as the Sulfur Source Leading to Enaminone-Based Alkynyl Sulfides under Ambient Conditions.

A highly efficient protocol for copper-catalyzed thio-alkynylation of enaminone-based thiocyanates with terminal alkynes under mild conditions has been developed. This scalable amino group-directed thio-alkynylation proceeds in the open air with a broad substrate scope and an excellent yield. The demonstrated synthetic transformation creates the opportunity for a wide variety of sulfur-containing useful materials. Gram-scale synthesis and further synthetic transformations of alkynyl sulfides highlight the potential utility of the method.

Biomechanical Analysis Using FEA and Experiments of Metal Plate and Bone Strut Repair of a Femur Midshaft Segmental Defect.

This investigation assessed the biomechanical performance of the metal plate and bone strut technique for fixing recalcitrant nonunions of femur midshaft segmental defects, which has not been systematically done before. A finite element (FE) model was developed and then validated by experiments with the femur in 15 deg of adduction at a subclinical hip force of 1 kN. Then, FE analysis was done with the femur in 15 deg of adduction at a hip force of 3 kN representing about 4 x body weight for a 75 kg person to examine clinically relevant cases, such as an intact femur plus 8 different combinations of a lateral metal plate of fixed length, a medial bone strut of varying length, and varying numbers and locations of screws to secure the plate and strut around a midshaft defect. Using the traditional "high stiffness" femur-implant construct criterion, the repair technique using both a lateral plate and a medial strut fixed with the maximum possible number of screws would be the most desirable since it had the highest stiffness (1948 N/mm); moreover, this produced a peak femur cortical Von Mises stress (92 MPa) which was below the ultimate tensile strength of cortical bone. Conversely, using the more modern "low stiffness" femur-implant construct criterion, the repair technique using only a lateral plate but no medial strut provided the lowest stiffness (606 N/mm), which could potentially permit more in-line interfragmentary motion (i.e., perpendicular to the fracture gap, but in the direction of the femur shaft long axis) to enhance callus formation for secondary-type fracture healing; however, this also generated a peak femur cortical Von Mises stress (171 MPa) which was above the ultimate tensile strength of cortical bone.

Integrated Modeling and Experimental Approaches to Control Silica Modification of Design Silk-Based Biomaterials.

Mineralized polymeric biomaterials provide useful options toward mechanically robust systems for some tissue repairs. Silks as a mechanically robust protein-based material provide a starting point for biomaterial options, particularly when combined with silica toward organic-inorganic hybrid systems. To further understand the interplay between silk proteins and silica related to material properties, we systematically study the role of three key domains in bioengineered spider silk fusion proteins with respect to ß-sheet formation and mineralization: (i) a core silk domain for materials assembly, (ii) a histidine tag for purification, and (iii) a silicification domain for mineralization. Computational simulations are used to identify the effect of each domain on the protein folding and accessibility of positively charged amino acids for silicification and predictions are then compared with experimental data. The results show that the addition of the silica and histidine domains reduces ß-sheet structure in the materials, and increases solvent-accessible surface area to the positive charged amino acids, leading to higher levels of silica precipitation. Moreover, the simulations show that the location of the charged biomineralization domain has small effect on the protein folding and consequently surface exposure of charged amino acids. Those surfaces display correlation with the amount of silicification in experiments. The results demonstrate that the exposure of the positively charged amino acids impacts protein function related to mineralization. In addition, processing parameters (solvating agent, the method of ß-sheet induction and temperature) affect protein secondary structure, folding and function. This integrated modeling and experimental approach provides insight into sequence-structure-function relationships for control of mineralized protein biomaterial structures.

Raman and Mossbauer spectroscopy and X-ray diffractometry studies on quenched copper-ferri-aluminates.

Four spinel ferrite compositions of the CuAl(x)Fe(2-x)O4, x = 0.0, 0.2, 0.4, 0.6, system prepared by usual double-sintering ceramic route and quenched (rapid thermal cooling) from final sintering temperature (1373 K) to liquid nitrogen temperature (80 K) were investigated by employing X-ray powder diffractometry, (57)Fe Mossbauer spectroscopy, and micro-Raman spectroscopy at 300 K. The Raman spectra collected in the wavenumber range of 100-1000 cm(-1) were analyzed in a systematic manner and showed five predicted modes for the spinel structure and splitting of A1g Raman mode into two/three energy values, attributed to peaks belonging to each ion (Cu(2+), Fe(3+), and Al(3+)) in the tetrahedral positions. The suppression of lower-frequency peaks was explained on the basis of weakening in magnetic coupling and reduction in ferrimagnetic behavior as well as increase in stress induced by square bond formation on Al(3+) substitution. The enhancement in intensity, random variation of line width, and blue shift for highest frequency peak corresponding to A1g mode were observed. The ferric ion (Fe(3+)) concentration for different compositions determined from Raman spectral analysis agrees well with that deduced by means of X-ray diffraction line-intensity calculations and Mossbauer spectral analysis. An attempt was made to determine elastic and thermodynamic properties from Raman spectral analysis and elastic constants from cation distribution.

Biomechanical analysis using infrared thermography of a traditional metal plate versus a carbon fibre/epoxy plate for Vancouver B1 femur fractures.

Traditional high-stiffness metal plates for Vancouver B1 femur shaft fractures below the tip of a hip implant can cause stress shielding, bone resorption, and implant loosening. This is the first study to compare the biomechanics of a traditional metal plate versus a low-stiffness carbon fibre/epoxy composite plate for this injury. A total hip replacement was implanted in two previously validated intact artificial femurs. Femurs were fitted with either a metal or composite plate and had a 5 mm fracture gap created to simulate a Vancouver B1 shaft fracture. Femurs were cyclically loaded using 5 Hz at 7° of adduction with an average axial load of 800 N (range = 400-1200 N). Overall mechanical stiffnesses and femur and plate thermographic stresses were obtained. Femur/metal plate stiffness (698 N/mm) was only 12% higher than femur/composite plate stiffness (625 N/mm). The femur with the composite plate had 22.7% higher combined average stress compared to the femur with the metal plate, having specific differences of 29.5% (anterior view), 33.9% (posterior view), 1.0% (medial view), and 26.4% (lateral view). The composite plate itself had an average 21.1% reduction in stress compared to the metal plate. The composite plate reduced stress shielding, yet provided adequate stiffness.

A reliable and effective method of DNA isolation from old human blood paper cards.

Blood paper cards provide an effective DNA storage method. In this study, we used three DNA dissolving reagents (Tris-EDTA [TE] buffer, Tris-HCl buffer, and water) and one common commercially available kit (DN131 from MRC Inc) to elute DNA from 105 human blood paper cards collected up to 10 years ago. These DNA samples were used as templates for amplification of a single nucleotide polymorphism (SNP, C125T) region of human caspase-12 by PCR and a specific Taqman genotyping assay using the same amount of DNA. We show that DNA isolated by Tris-HCl buffer has higher yield and quality in comparison to DN131 solution. PCR success rate to amplify caspase-12 C125T SNP using Tris-HCl is comparable to the method using DN131 (89.5% vs 87.6%). The Taqman genotyping success rate using Tris-HCl is higher than using DN131 (81.9% vs 70.5%). Using TE or water, PCR success rates are lower than using DN131 (73.3% [TE]; 72.4% [H2O]), but Taqman genotyping success rates are comparable to the method using DN131 (70.5% [TE]; 79.1% [H2O]). We concluded that using Tris-HCl is a reliable and effective method to elute DNA from old human blood paper cards. The crude DNA isolated by Tris-HCl can be used to study genetic polymorphisms in human populations.

The biomechanics of three different fracture fixation implants for distal femur repair in the presence of a tumor-like defect.

The femur is the most common long bone involved in metastatic disease. There is consensus about treating diaphyseal and epiphyseal metastatic lesions. However, the choice of device for optimal fixation for distal femur metaphyseal metastatic lesion remains unclear. This study compared the mechanical stiffness and strength of three different fixation methods. In 15 synthetic femurs, a spherical tumor-like defect was created in the lateral metaphyseal region, occupying 50% of the circumference of the bone. The defect was filled with bone cement and fixed with one of three methods: Group 1 (retrograde nail), Group 2 (lateral locking plate), and Group 3 (lateral nonlocking periarticular plate). Constructs were tested for mechanical stiffness and strength. There were no differences between groups for axial stiffness (Group 1, 1280 +/- 112 N/mm; Group 2, 1422 +/- 117 N/mm; and Group 3, 1403 +/- 122N/mm; p = 0.157) and offset torsional strength (Group 1, 1696 +/- 628N; Group 2, 1771 +/- 290N; and Group 3, 1599 +/- 253 N; p = 0.816). In the coronal plane, Group 2 (296 +/- 17 N/mm) had a higher stiffness than Group 1 (263 +/- 17N/mm; p = 0.018). In the sagittal plane, Group 1 (315 +/- 9 N/mm) had a higher stiffness than Group 3 (285 +/- 19 N/mm; p = 0.028). For offset torsional stiffness, Group 1 (256 +/- 23 N/mm) had a higher value than Group 3 (218 +/- 16 N/mm; p = 0.038). Group 1 had equivalent performance to both plating groups in two test modes, and it was superior to Group 3 in two other test modes. Since a retrograde nail (i.e. Group 1) would require less soft-tissue stripping in a clinical context, it may be the optimal choice for tumor-like defects in the distal femur.

The biomechanical effect of proximal tumor defect location on femur pathological fractures.

OBJECTIVES: The femur is the most common long bone affected by cancerous metastasis. Femoral tumor defects are known to induce pain and functional impairment in patients. Although prior studies exist evaluating the clinical and biomechanical effect of tumor defect size, no biomechanical studies have experimentally examined the risk of pathological fracture with respect to the anterior, posterior, medial, and lateral surfaces on which a proximal tumor defect is located on the femur. METHODS: Circular tumor-like defects of 40-mm diameter were created proximally in the subtrochanteric region on the Anterior (n = 5), Posterior (n = 5), Medial (n = 5), and Lateral (n = 5) sides of 20 synthetic femurs. Intact femurs served as a control group (n = 4). Femurs were tested for lateral, "offset" torsional, and axial stiffness, as well as axial strength. RESULTS: Lateral stiffnesses (range, 121-162 N/mm) yielded no differences between groups (P = 0.069). "Offset" torsional stiffnesses (range, 135-188 N/mm) demonstrated that the Medial group was less stiff than the Intact, Anterior, and Lateral groups (P ≤ 0.012). Axial stiffnesses (range, 1057-1993 N/mm) showed that the Medial group was less stiff than the Intact group (P = 0.006). Axial strengths (range, 3250-6590 N) for the Medial group were lower than Anterior (P = 0.001) and Posterior (P = 0.001) specimens, whereas the Lateral group had a lower strength than Anterior specimens (P = 0.019). No other statistical differences were noted. Axial failure of Medial and Lateral specimens involved the tumor-like defect in 100% of cases, whereas 100% of Intact femurs and 80% of Anterior and Posterior femur groups failed only through the neck. CONCLUSIONS: In 2 of 3 test modes, the Medial tumor-like defect group resulted in statistically lower stiffness values compared with Intact femurs and had lower strength than Anterior and Posterior groups in axial failure.

Biomechanical properties of an intact, injured, repaired, and healed femur: an experimental and computational study.

There is no "gold standard" treatment for femoral mid-shaft fractures near the tip of a hip implant. Moreover, no study has quantified the changes in a femur's mechanical properties from injury through to healing. The present aim was to predict overall stiffness and peak bone stress in the same femur after injury, repair, and healing with respect to its intact condition. Stage 1 was an intact femur. Stage 2 mimicked a femur with a hip stem. Stage 3 had a 5-mm fracture gap repaired with a plate and screws. Stage 4 represented complete fracture union. Experiments were done on a synthetic femur with strain gages and subjected to 1500 N of axial force. Finite element (FE) models were validated against experiments and then re-analyzed using a clinical-level force of 3000 N. At 1500 N, FE vs. experimental strains had excellent linear agreement (R=0.94; slope=0.97). At 3000 N, FE stiffnesses were 2167 N/mm (Stage 1), 2359 N/mm (Stage 2), 973 N/mm (Stage 3), and 3348 N/mm (Stage 4), showing that Stage 3 was the least stable compared to Stage 1. At 3000 N, FE bone stresses yielded peaks of 75.7 MPa at the load application point (Stage 1), 29.0 MPa near the hip implant tip (Stage 2), 126.3 MPa at the distal portion of the plate (Stage 3), and 69.3 MPa at the proximal portion of the plate (Stage 4), showing that Stage 3 was most vulnerable to re-injury compared to Stage 1. Stress shielding and high stresses were present not only after hip implantation and plating, but also after healing.

A biomechanical comparison of static versus dynamic lag screw modes for cephalomedullary nails used to fix unstable peritrochanteric fractures.

BACKGROUND: The gamma nail has an option to statically lock its lag screw (static mode) or to allow its lag screw to move within the nail to compress the intertrochanteric fracture (dynamic mode). The purpose of this study was to compare the biomechanical stiffness of static and dynamic lag screw modes for a cephalomedullary nail used to fix an unstable peritrochanteric fracture. METHODS: Unstable four-part peritrochanteric fractures were created in 30 synthetic femurs and fixed with Long Gamma 3 Nails. Mechanical tests were conducted for axial, lateral, and torsional stiffness with intact femurs, femur-nail constructs with static lag screw mode,and femur-nail constructs with dynamic lag screw mode. A paired Student's t test was used for all statistical comparisons between test groups. RESULTS: Axial and torsional stiffness of intact femurs was significantly greater than femur-nail constructs (p < 0.01 all comparisons),whereas lateral stiffness was significantly less (p < 0.01 all comparisons). Axial stiffness of the femur-nail construct was significantly greater (p < 0.01) in static mode (484.3 N/mm 80.2 N/mm) than in dynamic mode (424.1 N/mm 78.0 N/mm).Lateral stiffness was significantly greater (p < 0.01) in static mode (113.9 N/mm 8.4 N/mm) than in dynamic mode (109.5N/mm 8.8 N/mm). Torsional stiffness was significantly greater (p = 0.02) in dynamic mode (114.5 N/mm 28.2 N/mm) than in static mode (111.7 N/mm 27.0 N/mm). DISCUSSION: There is a 60 N/mm (12.4%) reduction in axial stiffness when the lag screw is in dynamic mode. Given the statistically significant reduction in axial and lateral stiffness with use of the dynamic mode, static lag screw mode should be further explored clinically for treatment of unstable peritrochanteric fractures.