ABSTRACT
The world population is steadily growing, exerting increasing pressure to feed in the future, which would need additional production of major crops. Challenges associated with changing and unpredicted climate (such as heat waves) are causing global food security threats. Cereal crops are a staple food for a large portion of the world's population. They are mostly affected by these environmentally generated abiotic stresses. Therefore, it is imperative to develop climate-resilient cultivars to support the sustainable production of main cereal crops (Rice, wheat, and maize). Among these stresses, heat stress causes significant losses to major cereals. These issues can be solved by comprehending the molecular mechanisms of heat stress and creating heat-tolerant varieties. Different breeding and biotechnology techniques in the last decade have been employed to develop heat-stress-tolerant varieties. However, these time-consuming techniques often lack the pace required for varietal improvement in climate change scenarios. Genome editing technologies offer precise alteration in the crop genome for developing stress-resistant cultivars. CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeat/Cas9), one such genome editing platform, recently got scientists' attention due to its easy procedures. It is a powerful tool for functional genomics as well as crop breeding. This review will focus on the molecular mechanism of heat stress and different targets that can be altered using CRISPR/Cas genome editing tools to generate climate-smart cereal crops. Further, heat stress signaling and essential players have been highlighted to provide a comprehensive overview of the topic.
ABSTRACT
Severe and combined nasal defects associated with trauma or neoplasm excision can cause significant functional and esthetic problems. To avoid nasal synechia following reconstructive surgeries, a nasal stent prosthesis is required to act as an internal scaffold to support the graft and residual tissues. The purpose of the stent is to maintain internal airway patency and to prevent collapse and contracture of the donor tissues. A conventional nasal stent prosthesis has disadvantages, including the difficulty in maintaining adequate thickness and internal patency during fabrication. Hence, this clinical report introduces the fabrication technique for 3- dimensionally printed polylactic acid nasal stent prostheses using extraoral scanning and photogrammetry methods.
ABSTRACT
ABSTRACT: Cleft palate leads to difficulty in suckling, speech abnormalities, dental problems, hearing loss and middle ear infections. Feeding plate acts as a barrier between the oral and nasal cavities allowing the normal development of jaws and enhanced nutritional supply to the patient. Fabrication of the feeding plate using digital means provide better adaptability due to the engagement of all the possible favourable anatomic undercuts, thereby, providing better retention. This case report discusses the hybrid technique including both the digital and conventional means for fabrication of a feeding plate to obturate the defect between the oral and nasal cavity.
Subject(s)
Cleft Lip , Cleft Palate , Infant , Humans , Cleft Palate/complications , Cleft Palate/surgeryABSTRACT
OBJECTIVE: To determine factors associated with magnetic resonance imaging (MRI) and noninvasive diagnostic angiography among children presenting to the emergency department (ED) with acute ischemic stroke. STUDY DESIGN: We performed a cross-sectional study using data from >50 US children's hospitals. We included children 29 days through 17 years old hospitalized from the ED with an International Classification of Diseases, Tenth Revision, Clinical Modification, diagnosis code for acute ischemic stroke between October 1, 2015, and November 30, 2022. We excluded children with a principal diagnosis code of trauma/external injury, without neuroimaging on day of presentation, and into-ED transfers. Our outcomes were defined as acquisition of MRI (vs computed tomography only) and angiography (vs no angiography) on day of presentation. We performed generalized linear mixed modeling with hospital as a random effect to determine the association of demographics, known comorbidities, and treatment factors with each outcome. RESULTS: We included 1601 children. In multivariable analysis, younger age, mechanical ventilation, and Black race were associated with lower odds of MRI acquisition, whereas history of moyamoya disease and sickle cell disease were associated with greater odds. Younger age, mechanical ventilation, Hispanic ethnicity, Black race, other races, history of metabolic disease, and history of seizures were associated with lower odds of angiography. CONCLUSIONS: Younger and non-White children experienced lower odds of MRI and angiography, which may be driven by health system limitations or provider implicit biases or both. Our results expose risk factors for underdiagnosis of ischemic stroke and provide opportunities to tailor institutional pathways reflective of underlying pathophysiology.
Subject(s)
Ischemic Stroke , Magnetic Resonance Imaging , Neuroimaging , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Cerebral Angiography , Critical Pathways , Cross-Sectional Studies , Emergency Service, Hospital/statistics & numerical data , Ischemic Stroke/diagnostic imaging , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed , United States/epidemiologyABSTRACT
BACKGROUND: Perrault Syndrome (PRLTS) is a rare, autosomal recessive disorder that presents with bilateral sensorineural hearing loss in all patients and gonadal dysfunction in females. It has been linked to variants in CLPP, ERAL1, HARS2, HSD17B4, LARS2, and TWNK genes. All reported cases due to TWNK variants have included neurologic features, such as ataxia and axonal sensorimotor neuropathy. CASE PRESENTATION: A 4.5-year-old female presented to neuromuscular clinic due to ataxia. Neurological examination revealed truncal ataxia and steppage gait, reduced deep tendon reflexes, and axonal sensorimotor polyneuropathy. Auditory brainstem response testing revealed an uncommon type of sensorineural hearing loss known as auditory neuropathy/auditory synaptopathy (AN/AS) affecting both ears. Magnetic Resonance Imaging (MRI) revealed subtle cauda equina enhancement. Nerve conduction studies led to a provisional diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP), and intravenous immune globulin (IVIG) was initiated. The patient was unresponsive to treatment, thus whole exome testing (WES) was conducted in tandem with IVIG weaning. WES revealed a compound heterozygous state with two variants in the TWNK gene and a diagnosis of Perrault Syndrome was made. CONCLUSIONS: Perrault Syndrome should be considered in the differential for children who present with bilateral sensorineural hearing loss, axonal polyneuropathy, and ataxia. Further examination includes testing for ovarian dysgenesis and known PRLTS genetic variants.
Subject(s)
Amino Acyl-tRNA Synthetases , Hearing Loss, Sensorineural , Polyneuropathies , Child, Preschool , Female , Humans , Amino Acyl-tRNA Synthetases/genetics , Ataxia , Hearing Loss, Sensorineural/genetics , Immunoglobulins, Intravenous/genetics , MutationABSTRACT
Sugarcane (Saccharum spp.) is a widely cultivated crop that fulfils approximately 75% of the sucrose demand worldwide. Owing to its polyploidy and complex genetic nature, it is difficult to identify and map genes related to complex traits, such as sucrose content. However, association mapping is one of the alternatives for identifying genes or markers for marker-assisted selection. In the present study, EST-SSR primers were obtained from in silico studies. The functionality of each primer was tested using Blast2Go software, and 30 EST-SSR primers related to sugar content were selected. These markers were validated using association analysis. A total of 70 F1 diverse genotypes for sugar content were phenotypes with two check lines. All parameters related to sugar content were recorded. The results showed a significant variation between the genotypes for sugar yield traits such as Brix value, purity, and sucrose content, etc. Correlation studies revealed that the Brix%, sucrose content, and sucrose recovery were significantly correlated. An association analysis was performed using mixed linear model to avoid false positive associations. The association analysis revealed that the SEM 407 marker was significantly associated with Brix% and sucrose content. The SEM 407 primers are putatively related to diphosphate-fructose-6-phosphate 1-phosphotransferase which is associated with Brix% and sucrose content. This functional marker can be used for marker-assisted selection for sugar yield traits in sugarcane that could accelerate the sugarcane breeding program.
ABSTRACT
Type 2 diabetes mellitus is a bipolar metabolic disorder characterized by abnormalities in insulin production from ß-cells and insulin resistance. Thiazolidinediones are potent anti-diabetic agents that act through the modulation of the peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor. However, their full agonistic activity leads to severe side effects by stabilizing Helix12 through strong hydrogen bonding with the TYR473 residue. Partial and selective PPARγ modulators (GW0072, GQ16, VSP-51, MRL-20, MBX-213, INT131) have demonstrated superior results compared to full agonists without causing adverse effects, as reported in existing data. To address this uncertainty and advance therapeutic options, we identified and designed a novel class of compounds (A1-A23) based on a hybrid structure combining phenolic and Thiazolidine-4-one's moieties. Our rational drug design strategy incorporated structural-activity relationship principle, and validated the docking studies through calculated the root mean square deviation. Additionally, we conducted molecular docking, binding energy, molecular dynamics simulations, and post-molecular dynamics calculations to evaluate the dynamics behavior between the ligands and protein. The selected ligands demonstrated highly favorable docking scores and binding energies, comparable to the co-crystal (rosiglitazone) such as A12 (-13.9 kcal/mol and -86.2 kcal/mol), A1 (-11.1 kcal/mol and -79.5 kcal/mol), A13 (-11.3 kcal/mol and -91.4 kcal/mol), and the co-crystal itself (-9.8 kcal/mol and -76 kcal/mol), respectively. Finally, the MD revealed that, the selected ligands were equally contributed for stabilization of Helix12 and ß-sheets. It was concluded, the designed ligands (A12, A1, and A13) exhibited weaker hydrogen-bond interactions with specific residue TYR473 which partially modulated the PPARγ protein.Communicated by Ramaswamy H. Sarma.
ABSTRACT
The rehabilitation of facial deformities is a challenging endeavour that necessitates customising the procedure for each patient. Significant physical and psychological impacts might arise as a result of the deformity in the orofacial region. Post-COVID rhino-orbital mucormycosis has led to rise in extraoral and intraoral defects since 2020. To avoid further surgery, an economical maxillofacial prosthesis is an excellent choice as it is aesthetic, durable, long-lasting and retentive. This case report describes the prosthetic rehabilitation of the patient with post-COVID mucormycosis maxillectomy and orbital exenteration using a magnet-retained closed bulb hollow acrylic obturator and room-temperature vulcanising silicone orbital prosthesis. To enhance retention, a spectacle and medical-grade adhesive were also used.
Subject(s)
COVID-19 , Mucormycosis , Humans , Mucormycosis/diagnosis , Mucormycosis/etiology , Mucormycosis/surgery , Magnets , Nigeria , Prostheses and ImplantsABSTRACT
Loss of a sense organ, such as an eye in situations of orbital involvement, or any other bodily part, such as the maxilla or palate, might make one more dependent on others for care and affect how they perceive themselves in society. The prosthetic rehabilitation of large mid-facial defects is a challenging task due to the varied size and shape of the defect. Confluent maxillary and orbital abnormalities are best restored with prosthetic means by creating a comfortable, aesthetically pleasing prosthesis that allows for the restoration of speech, deglutition, and mastication. The retention of any prosthesis is must for it to be successful. The hollow orbital conformer described in this case presentation aids in reducing the weight of the prosthesis, thereby enhancing the retention of the prosthesis. This clinical case presentation highlights the aesthetic and functional rehabilitation using a combined obturator-orbital prosthesis connected using intraoral magnets.
ABSTRACT
The unfortunate loss of all or part of a finger caused by traumatic amputation has a negative impact on physical and psychological well-being of a person. Thus an aesthetic prosthesis can offer psychological, functional and rehabilitative advantages. One of the major problems with the prosthetic replacement of a partially amputated finger is inadequate retention of the prosthesis and there are numerous means to enhance the retention. The most routinely used are adhesives, adhesive tape, magnets and implants. The present article describes a technique which utilizes room temperature vulcanizing silicone (RTV) as a prosthetic material retained by preformed artificial rings. Such treatment can be opted for in cases of financial constraints.
Subject(s)
Fingers , Silicone Elastomers , Humans , Prosthesis Design , Fingers/surgery , Prosthesis Implantation , EstheticsABSTRACT
Effective esthetic rehabilitation requires a proper treatment planning in addition to the associated diagnostic wax-up. For anterior rehabilitation, most dentists favor conservative and esthetic treatments, such as indirect laminate veneer restorations which can be partial- or full-ceramic anterior crowns according to the clinical situations. After the introduction of technologies such as intraoral scanners, dental software for digital restoration design, and additive manufacturing (three-dimensional printing), these techniques further enhanced the digital workflow of restorative therapy. These technologies also fabricate prosthesis with natural esthetics and marginal integrity. This case series discusses the conventional and digitally fabricated full- and partial-ceramic veneers for discolored and misaligned anterior teeth after the fabrication of corresponding diagnostic wax-up.
ABSTRACT
Rationale: COVID-19 has led to a resurgence in cases of mucormycosis, especially the rhino-orbital form affecting the oral cavity, nasal, orbital and cerebral regions. Patient Concerns: The surgical treatment in this patient led to the exenteration of orbital contents and segmental maxillectomy of the affected side leading to facial disfigurement and inability to masticate. Diagnosis: A combined mucormycosis-associated oro-orbital defect was present leading to a communication between oral and orbital cavities. Treatment: Rehabilitation utilising digital technology for removable prosthesis was planned for the combined orbital and oral defect. Outcomes: The independent intraoral and orbital prosthesis reduced the mobility of the orbital prosthesis while performing functional movements. The advancements in digital technology led to the convenient and resilient fabrication of prostheses for large facial defects. Take-away Lessons: The prosthetic rehabilitation of a continuous orbital and oral defect with a hybrid of both digital and conventional means provided an aesthetic, feasible and financially sound solution to the patient.
ABSTRACT
Caloric restriction and acute fasting are known to reduce seizures but through unclear mechanisms. mTOR signaling has been suggested as a potential mechanism for seizure protection from fasting. We demonstrate that brain mTORC1 signaling is reduced after acute fasting of mice and that neuronal mTORC1 integrates GATOR1 complex-mediated amino acid and tuberous sclerosis complex (TSC)-mediated growth factor signaling. Neuronal mTORC1 is most sensitive to withdrawal of leucine, arginine, and glutamine, which are dependent on DEPDC5, a component of the GATOR1 complex. Metabolomic analysis reveals that Depdc5 neuronal-specific knockout mice are resistant to sensing significant fluctuations in brain amino acid levels after fasting. Depdc5 neuronal-specific knockout mice are resistant to the protective effects of fasting on seizures or seizure-induced death. These results establish that acute fasting reduces seizure susceptibility in a DEPDC5-dependent manner. Modulation of nutrients upstream of GATOR1 and mTORC1 could offer a rational therapeutic strategy for epilepsy treatment.
Subject(s)
Fasting , GTPase-Activating Proteins , Mechanistic Target of Rapamycin Complex 1 , Seizures , Amino Acids , Animals , GTPase-Activating Proteins/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Mice , Mice, Knockout , Seizures/metabolismABSTRACT
Biallelic pathogenic variants in SZT2 result in a neurodevelopmental disorder with shared features, including early-onset epilepsy, developmental delay, macrocephaly, and corpus callosum abnormalities. SZT2 is as a critical scaffolding protein in the amino acid sensing arm of the mTORC1 signalling pathway. Due to its large size (3432 amino acids), lack of crystal structure, and absence of functional domains, it is difficult to determine the pathogenicity of SZT2 missense and in-frame deletions, but these variants are increasingly detected and reported by clinical genetic testing in individuals with epilepsy. To exemplify this latter point, here we describe a cohort of 12 individuals with biallelic SZT2 variants and phenotypic overlap with SZT2-related neurodevelopmental disorders. However, the majority of individuals carried one or more SZT2 variants of uncertain significance (VUS), highlighting the need for functional characterization to determine, which, if any, of these VUS were pathogenic. Thus, we developed a novel individualized platform to identify SZT2 loss-of-function variants in the context of mTORC1 signalling and reclassify VUS. Using this platform, we identified a recurrent in-frame deletion (SZT2 p.Val1984del) which was determined to be a loss-of-function variant and therefore likely pathogenic. Haplotype analysis revealed that this single in-frame deletion is a founder variant in those of Ashkenazi Jewish ancestry. Moreover, this approach allowed us to tentatively reclassify all of the VUS in our cohort of 12 individuals, identifying five individuals with biallelic pathogenic or likely pathogenic variants. Clinical features of these five individuals consisted of early-onset seizures (median 24 months), focal seizures, developmental delay and macrocephaly similar to previous reports. However, we also show a widening of the phenotypic spectrum, as none of the five individuals had corpus callosum abnormalities, in contrast to previous reports. Overall, we present a rapid assay to resolve VUS in SZT2, identify a founder variant in individuals of Ashkenazi Jewish ancestry, and demonstrate that corpus callosum abnormalities is not a hallmark feature of this condition. Our approach is widely applicable to other mTORopathies including the most common causes of the focal genetic epilepsies, DEPDC5, TSC1/2, MTOR and NPRL2/3.
Subject(s)
Epilepsies, Partial , Epilepsy , Megalencephaly , Epilepsy/genetics , Humans , Mechanistic Target of Rapamycin Complex 1/genetics , Megalencephaly/genetics , Nerve Tissue Proteins/genetics , Tumor Suppressor Proteins/geneticsABSTRACT
One of the most challenging esthetic concerns in dentistry is conservative replacement of the missing anterior teeth. Although implants are considered to be a better treatment option for rehabilitation of such patients, resin-bonded bridges (RBBs) can conservatively restore the missing teeth and have thus gained popularity over the years. It consists of an artificial tooth with a wing-like extension that is cemented to the adjacent teeth. There are various types of RBBs among which Maryland bridge is the simplest and the popular most due to its micromechanical retention enabled by acid etching of both tooth and metal retainer. It can be fabricated by various techniques and materials. In this case reports, we have discussed about two unique designs of Maryland bridge fabricated by two different materials (Porcelain-fused metal and Graphene) and utilizing two different techniques (conventional and digital).
ABSTRACT
Leigh syndrome, a mitochondrial disease, can be modeled in mice with a deficiency in mitochondrial complex I that results in a decreased NAD+/NADH ratio. In this issue of Cell Metabolism, Liu et al. (2021) identify glycerol-3-phosphate (Gro3P) biosynthesis as a method for regenerating cytosolic NAD+ to ameliorate pathology in this mitochondrial disease model.
Subject(s)
Mitochondrial Diseases , NAD , Animals , Cytosol/metabolism , Homeostasis , Mice , Mitochondria , Mitochondrial Diseases/metabolism , NAD/metabolismABSTRACT
Osteoclasts differentiate from hematopoietic cells and resorb the bone in response to various signals, some of which are received directly from noncellular elements of the bone. In vitro, adherence to the bone triggers the reduction of cell-cell fusion events between osteoclasts and the activation of osteoclasts to form unusual dynamic cytoskeletal and membrane structures that are required for degrading the bone. Integrins on the surface of osteoclasts are known to receive regulatory signals from the bone matrix. Regulation of the availability of these signals is accomplished by enzymatic alterations of the bone matrix by protease activity and phosphorylation/dephosphorylation events. Other membrane receptors are present in osteoclasts and may interact with as yet unidentified signals in the bone. Bone mineral has been shown to have regulatory effects on osteoclasts, and osteoclast activity is also directly modulated by mechanical stress. As understanding of how osteoclasts and other bone cells interact with the bone has emerged, increasingly sophisticated efforts have been made to create bone biomimetics that reproduce both the structural properties of the bone and the bone's ability to regulate osteoclasts and other bone cells. A more complete understanding of the interactions between osteoclasts and the bone may lead to new strategies for the treatment of bone diseases and the production of bone biomimetics to repair defects.
Subject(s)
Bone Matrix/metabolism , Bone Resorption/metabolism , Bone and Bones/metabolism , Cell Membrane/metabolism , Osteoclasts/metabolism , Actins/chemistry , Animals , Biomimetics , Calcium/metabolism , Cell Adhesion Molecules/metabolism , Cell Differentiation , Gene Expression Regulation , Humans , Hyaluronan Receptors/metabolism , Immunoglobulins/metabolism , Integrins/metabolism , Low Density Lipoprotein Receptor-Related Protein-1/metabolism , Osteopontin/metabolism , Phosphorylation , Podosomes/metabolism , Protein Binding , Stress, Mechanical , Synaptotagmins/metabolismABSTRACT
3-Hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency is a rare mitochondrial disorder of valine metabolism which may present with motor delay, hypotonia, ataxia, dystonia, seizures poor feeding, and organic aciduria. Neuroimaging findings include signal abnormalities of the deep gray matter, particularly the globus pallidi, and cerebral peduncles. We report a 15-month-old male patient with HIBCH deficiency who presented with paroxysmal tonic upgaze of infancy, motor delay, and hypotonia. MRI revealed characteristic bilateral, symmetric signal abnormalities in the basal ganglia and a mutation in HIBCH was confirmed with whole exome sequencing. HIBCH should be a consideration in patients with Leigh-like features, especially if neuroimaging changes primarily affect the globus pallidi. Recognition of this pattern may help guide targeted testing and expedite the diagnosis and treatment of this rare disease.
ABSTRACT
Recent work by Licznerski et al. suggests that mutant FMRP linked to Fragile-X syndrome elevates the inner mitochondrial membrane proton leak, leading to increased metabolism and changes in protein synthesis that trigger impaired synaptic maturation and autistic behaviors.