A band gap and photoluminescence properties engineering in BaO semiconductor for ultraviolet (UV) photodetector applications: A comprehensive role of co-doping.

We report on ultra-violet (UV) photodetectors based on BaO nanoparticles by the detailed investigation of band gap and photoluminescence properties. The BaO nanomaterials were fabricated by the modified sol-gel technique. The innovation of co-doping can modulate the photoluminescence or sensing properties by narrowing the band gap related to enhancing the high carrier concentration, higher electronic lifetime, and low carriers recombination. It is investigated that the BaO nanoparticles with co-doping reveals a highly reduced band gap and exceptional photoluminescence properties as compared to the pristine BaO nanoparticles due to hindering carrier,s recombination for Ultra-violet (UV) photodetectors. The optical studies revealed that the addition of co-dopants in BaO host material creates new energy sites, so the band gap declines up to 1.31 eV as compared to that of pristine BaO (1.36 eV). The photoluminescence properties recorded with photoluminescence (PL) spectroscopy were recorded which revealed the decrease in PL intensity due to the hindering of carriers recombination with the addition of co-dopant metal ions. Furthermore, the inclusion of co-dopant metals results in an improvement in electrical conductivity because of a decline in carrier recombination, according to an I-V characteristic study. This factor contributes to enhance the photoluminescence properties of BaO which, in turn, contributes to enhance the sensing capability of the photodetector device. These obtained features modify optoelectronic properties are far superior as compared to that of previously reported literature on BaO nanomaterials, and the synthesized BaO semiconductor material becomes a potential candidate for efficient use in the ultraviolet (UV) photodetectors device applications.

Structural performance of FRP composite bars reinforced rubberized concrete compressive members: Tests and numerical modeling.

Waste tyre rubber has become an environmental and health concern that needs to be sustainably managed to avoid fire hazards and save natural resources. This research work aims to study the structural behavior of glass fiber reinforced polymer (glass-FRP) reinforced rubberized concrete (GRC) compressive elements under monotonic axial compression loads. Nine GRC circular compressive elements with different axial and crosswise reinforcement ratios were fabricated. All the elements were 300 mm in diameter and 1200 mm in height. A 3D nonlinear finite element equation (FEM) was suggested for the GRC compressive elements using a commercial package ABAQUS. A parametric study has been done to examine the effect of various parameters of GRC elements. The test outcomes revealed that the ductility of GRC elements ameliorated with the lessening in the spaces of glass-FRP ties. The addition of rubberized concrete improved the ductility of GRC elements. The damage to GRC elements occurred due to the vertical cracking along the height of the elements. The estimates of FEM were in close agreement with the test outcomes. The suggested empirical equation depending on the 600 test elements, which considered the lateral confinement effect of FRP ties, presented higher accuracy than previous equations.

The interleukin-11 receptor variant p.W307R results in craniosynostosis in humans.

Craniosynostosis is characterized by the premature fusion and ossification of one or more of the sutures of the calvaria, often resulting in abnormal features of the face and the skull. In cases in which growth of the brain supersedes available space within the skull, developmental delay or cognitive impairment can occur. A complex interplay of different cell types and multiple signaling pathways are required for correct craniofacial development. In this study, we report on two siblings with craniosynostosis and a homozygous missense pathogenic variant within the IL11RA gene (c.919 T > C; p.W307R). The patients present with craniosynostosis, exophthalmos, delayed tooth eruption, mild platybasia, and a basilar invagination. The p.W307R variant is located within the arginine-tryptophan-zipper within the D3 domain of the IL-11R, a structural element known to be important for the stability of the cytokine receptor. Expression of IL-11R-W307R in cells shows impaired maturation of the IL-11R, no transport to the cell surface and intracellular retention. Accordingly, cells stably expressing IL-11R-W307R do not respond when stimulated with IL-11, arguing for a loss-of-function mutation. In summary, the IL-11R-W307R variant, reported here for the first time to our knowledge, is most likely the causative variant underlying craniosynostosis in these patients.

Investigation of structural, electronic and optical properties of two-dimensional MoS2-doped-V2O5 composites for photocatalytic application: a density functional theory study.

In the present research, the structural, electronic and optical properties of transition metal dichalcogenide-doped transition metal oxides MoS2-doped-V2O5 with various doping concentrations (x = 1-3%) of MoS2 atoms are studied by using first principles calculation. The generalized gradient approximation Perdew-Burke-Ernzerhof simulation approach is used to investigate the energy bandgap (Eg) of orthorhombic structures. We examined the energy bandgap (Eg) decrement from 2.76 to 1.30 eV with various doping (x = 1-3%) of molybdenum disulfide (MoS2) atoms. The bandgap nature shows that the material is a well-known direct bandgap semiconductor. MoS2 doping (x = 1-3%) atoms in pentoxide (V2O5) creates the extra gamma active states which contribute to the formation of conduction and valance bands. MoS2-doped-V2O5 composite is a proficient photocatalyst, has a large surface area for absorption of light, decreases the electron-hole pairs recombination rate and increases the charge transport. A comprehensive study of optical conductivity reveals that strong peaks of MoS2-doped-V2O5 increase in ultraviolet spectrum region with small shifts at larger energy bands through increment doping x = 1-3% atoms of MoS2. A significant decrement was found in the reflectivity due to the decrement in the bandgap with doping. The optical properties significantly increased by the decrement of bandgap (Eg). Two-dimensional MoS2-doped-V2O5 composite has high energy absorption, optical conductivity and refractive index, and is an appropriate material for photocatalytic applications.

Shifts in the Distribution Range and Niche Dynamics of the Globally Threatened Western Tragopan (Tragopan melanocephalus) Due to Climate Change and Human Population Pressure.

The impact of a changing climate, particularly global warming, often harms the distribution of pheasants, particularly those with limited endemic ranges. To effectively create plans of action aimed at conserving species facing threats such as the Western Tragopan, (Tragopan melanocephalus; Gray, 1829; Galliformes, found in the western Himalayas), it is crucial to understand how future distributions may be affected by anticipated climate change. This study utilized MaxEnt modeling to assess how suitable the habitat of the targeted species is likely to be under different climate scenarios. While similar studies have been conducted regionally, there has been no research on this particular endemic animal species found in the western Himalayas throughout the entire distribution range. The study utilized a total of 200 occurrence points; 19 bioclimatic, four anthropogenic, three topographic, and a vegetation variable were also used. To determine the most fitting model, species distribution modeling (SDM) was employed, and the MaxEnt calibration and optimization techniques were utilized. Data for projected climate scenarios of the 2050s and 2070s were obtained from SSPs 245 and SSPs 585. Among all the variables analyzed; aspect, precipitation of coldest quarter, mean diurnal range, enhanced vegetation index, precipitation of driest month, temperature seasonality, annual precipitation, human footprint, precipitation of driest quarter, and temperature annual range were recognized as the most influential drivers, in that order. The predicted scenarios had high accuracy values (AUC-ROC > 0.9). Based on the feedback provided by the inhabitants, it was observed that the livability of the selected species could potentially rise (between 3.7 to 13%) in all projected scenarios of climate change, because this species is relocating towards the northern regions of the elevation gradient, which is farther from the residential areas, and their habitats are shrinking. The suitable habitats of the Tragopan melanocephalus in the Himalayan region will move significantly by 725 m upwards, because of predicted climate change. However, the fact that the species is considered extinct in most areas and only found in small patches suggests that further research is required to avert a further population decline and delineate the reasons leading to the regional extinction of the species. The results of this study can serve as a foundation for devising conservation strategies for Tragopan melanocephalus under the changing climate and provide a framework for subsequent surveillance efforts aimed at protecting the species.

Lyophilization Based Isolation of Exosomes.

Exosomes are nanoscale extracellular vesicles which regulate intercellular communication. They have great potential for application in nanomedicine. However, techniques for their isolation are limited by requirements for advanced instruments and costly reagents. In this study, we developed a lyophilization-based method for isolating exosomes from cultured cells. The isolated exosomes were characterized for protein content using Bradford assay, and for size distribution and shape using scanning electron microscopy (SEM) and nanoparticles tracking analysis (NTA). In addition, CD63, CD9, CD81, HSP70 and TSG101 were evaluated as essential exosomal surface markers using Western blot. Drug loading and release studies were performed to confirm their drug delivery properties using an in vitro model. Exosomes were also loaded with commercial dyes (Cy5, Eosin) for the evaluation of their drug delivery properties. All these characterizations confirmed successful exosome isolation with measurements of less than 150 nm, having a typical shape, and by expressing the known exosome surface protein markers. Finally, tyrosine kinase inhibitors (dasatinib and ponatinib) were loaded on the exosomes to evaluate their anticancer effects on leukemia cells (K562 and engineered Ba/F3-BCR-ABL) using MTT and Annexin-PI assays. The expression of MUC1 protein on the exosomes isolated from MCF-7 cells also indicated that their potential diagnostic properties were intact. In conclusion, we developed a new method for exosome isolation from cultured cells. These exosomes met all the essential requirements in terms of characterization, drug loading and release ability, and inhibition of proliferation and apoptosis induction in Ph+ leukemia cells. Based on these results, we are confident in presenting the lyophilization-based exosome isolation method as an alternative to traditional techniques for exosome isolation from cultured cells.

A homozygous founder variant in PDE2A causes paroxysmal dyskinesia with intellectual disability.

Intellectual developmental disorder with paroxysmal dyskinesia or seizures (IDDPADS, OMIM#619150) is an ultra-rare childhood-onset autosomal recessive movement disorder manifesting paroxysmal dyskinesia, global developmental delay, impaired cognition, progressive psychomotor deterioration and/or drug-refractory seizures. We investigated three consanguineous Pakistani families with six affected individuals presenting overlapping phenotypes partially consistent with the reported characteristics of IDDPADS. Whole exome sequencing identified a novel missense variant in Phosphodiesterase 2A (PDE2A): NM_002599.4: c.1514T > C p.(Phe505Ser) that segregated with the disease status of individuals in these families. Retrospectively, we performed haplotype analysis that revealed a 3.16 Mb shared haplotype at 11q13.4 among three families suggesting a founder effect in this region. Moreover, we also observed abnormal mitochondrial morphology in patient fibroblasts compared to controls. Belonging to diverse age groups (13 years-60 years), patients presented paroxysmal dyskinesia, developmental delay, cognitive abnormalities, speech impairment, and drug-refractory seizures with variable onset of disease (as early as 3 months of age to 7 years). Together with the previous reports, we observed that intellectual disability, progressive psychomotor deterioration, and drug-refractory seizures are consistent outcomes of the disease. However, permanent choreodystonia showed variability. We also noticed that the later onset of paroxysmal dyskinesia manifests severe attacks in terms of duration. Being the first report from Pakistan, we add to the clinical and mutation spectrum of PDE2A-related recessive disease raising the total number of patients from six to 12 and variants from five to six. Together, with our findings, the role of PDE2A is strengthened in critical physio-neurological processes.

Effect of laser irradiated silver doped polystyrene/polyethylene terephthalate (PET) thin film for solar cell applications.

In the current research, the resist action of silver-doped polystyrene/polyethylene terephthalate (PET) solar thin film towards laser irradiation was observed. Moreover, silver-doped polystyrene nanoparticles were synthesized via a chemical technique while the PET film was purchased from the commercial market. Nd:YAG pulsed laser has been used to irradiate the samples at 2 minutes, 4 minutes, and 6 minutes respectively. The XRD (X-ray diffraction) pattern shows that silver-doped polystyrene peak at around angle θ = 26° tends to decrease after the bombardment of Nd:YAG pulsed laser. This indicates that the crystallinity of PET film decreased after laser irradiation. The Raman spectra have revealed the zwitter characteristics of silver-doped polystyrene are shifting of bands at 1380 cm-1 and 1560 cm-1 upon laser irradiation. For PET film, the Raman spectra showed that the exposed regions tend to change to cross-linking/chain-scissoring at 2 minutes and 4 minutes of irradiation. The surface roughness first increases and decreases upon irradiation. These results indicate that silver-doped polystyrene/polyethylene terephthalate (PET) thin film is appropriate for solar cell applications.

Medicinal waterbirds in the traditional healthcare system: an assessment of biodiversity-cultural linkages in Eastern Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Eastern Khyber Pakhtunkhwa is home to a vast range of medicinal and edible waterbird species due to its diverse geographical environment. Waterbird species have been used for various ailments and cultural practices since ancient times, while ethno-pharmacological applications and cultural uses of waterbird species in this area have seldom been documented. This study is the first ethnomedicinal and cultural assessment of waterbird species, and the first compilation and listing of all known data on these species in Eastern Khyber Pakhtunkhwa, Pakistan. METHODS: Interviews and questionnaires were used to collect data from native respondents (N = 100). To analyze the data, principal component analysis (PCA), relative frequency of citation (RFC), fidelity level (FL%), relative popularity level (RPL), rank order priority, and similarity index were used. RESULTS: In total, 64 waterbird species were utilized in cultural practices, of which 40 species are used to cure different infectious and chronic diseases such as cold, cough, flu, fever, respiratory disorders, asthma, TB, gastric ulcers, kidney stones, male impotency, obesity, paralysis, piles, cancer, arthritis, body pain, and weakness. PCA showed significant differences in the use of waterbird species among the local inhabitants of the study area, separated along the axis-2 (p < 0.05). The FL% of waterbird species varied from 12 to 100%. 100% FL was analyzed for four waterbird species, i.e., Charadrius mongolus (cold), Gallicrex cinerea (asthma), Anas platyrhynchos (cancer), and Esacus recurvirostris (body weakness). In this study, Mallard (Anas platyrhynchos) was the most popular species used in the healthcare system of Eastern Khyber Pakhtunkhwa, with high RFC (4.06), FL% (100), and RPL (1.0) values. CONCLUSION: We concluded that waterbird species are more used for medicine and food purposes in the study area. However, in vitro/in vivo assessment of biochemical activities of waterbird species with a maximum FL% might be significant to produce novel drugs. Recent research shows important ethno-ornithological information about native people and their links with waterbird species, which might be helpful for the sustainable use of waterbird diversity in the research area.

Process evaluation of chest camps for increased tuberculosis case finding in Punjab, Pakistan.

BACKGROUND: To contribute to the World Health Organization's End TBStrategy, the active tuberculosis (TB) case-finding approach has been proven effective. METHODS: A total of 66 chest camps were organised for patients in 15 selected districts in Punjab, Pakistan, in 2017. A mixed-method process evaluation was conducted in four randomly selected districts to evaluate the use of chest camps for active TB case finding to reach the maximum number of people with TB and to assess the implementation outcomes, such as effectiveness, feasibility, fidelity, and costs. RESULTS: Results indicated that 1458 attendees visited 24 chest camps in four selected districts. Among attendees, 297 presumptive cases were found and smear-tested; and 34 of the smear-tested were diagnosed as smear-positive TB patients. The prevalence of smear-positive TB patients among the chest camp participants was found to be 2.3%. The findings from interviews showed that preparation of chest camp activities, especially the involvement of community leaders, was found to be effective in achieving the desired level of attendance. The respondents found attending the chest camps for TB symptoms feasible and acceptable. The chest camp costs approximately US$280, including the pre-camp mobilisation events, whereas the cost per TB-positive patient was found to be US$197.64. CONCLUSIONS: The higher number of attendees without TB symptoms, the low proportion of smear-negative case registrations; and relatively high unit cost (per patient detected) were the areas identified for further attention. The study supports the continuation of chest camp activity, with further attention required for quality and efficiency concerns.

Numerical investigation of the effect of spanwise length and mesh density on flow around cylinder at Re = 3900 using LES model.

Flow around circular cylinder has been extensively studied by researchers for several decades due to its wide range of engineering applications such as in heat exchangers, marine cables, high rise building, chimneys, and offshore structures. The lack of clear understanding of the unsteady flow dynamics in the wake of circular cylinder and high computational cost are still an area of high interest amongst the researchers. The aim of the current study is to investigate the effect of variation in spanwise length and grid resolution in the spanwise direction on the recirculation length, separation angle of wake flow by performing large eddy simulations (LES). This study is an extension to previous work by Khan, NB et al, 2019 in which the spanwise length is restricted to 4D only. In current study, the spanwise length is changed from 0.5D to 8D where D is diameter of cylinder and mesh resolution in the spanwise direction is changed from 1 to 80 elements in the present study. The recirculation length, separation angle and wake characteristics are analyzed in detail. It is concluded that after getting optimize spanwise length, mesh resolution in the spanwise direction is the only parameter contributing toward better result.

A recurrent rare intronic variant in CAPN3 alters mRNA splicing and causes autosomal recessive limb-girdle muscular dystrophy-1 in three Pakistani pedigrees.

Autosomal recessive limb-girdle muscular dystrophy-1 (LGMDR1) is an autosomal recessive disorder characterized by progressive weakness of the proximal limb and girdle muscles. Biallelic mutations in CAPN3 are reported frequently to cause LGMDR1. Here, we describe 11 individuals from three unrelated consanguineous families that present with typical features of LGMDR1 that include proximal muscle wasting, weakness of the upper and lower limbs, and elevated serum creatine kinase. Whole-exome sequencing identified a rare homozygous CAPN3 variant near the exon 2 splice donor site that segregates with disease in all three families. mRNA splicing studies showed partial retention of intronic sequence and subsequent introduction of a premature stop codon (NM_000070.3: c.379 + 3A>G; p.Asp128Glyfs*15). Furthermore, we observe reduced CAPN3 expression in primary dermal fibroblasts derived from an affected individual, suggesting instability and/or nonsense-mediated decay of mutation-bearing mRNA. Genome-wide homozygosity mapping and single-nucleotide polymorphism analysis identified a shared haplotype and supports a possible founder effect for the CAPN3 variant. Together, our data extend the mutational spectrum of LGMDR1 and have implications for improved diagnostics for individuals of Pakistani origin.

The Effect of Ca Dopant on the Electrical and Dielectric Properties of BaTi4O9 Sintered Ceramics.

The current research examines the impact of Ca2+ substitution on the phase and electrical properties of (Ba1-xCax)Ti4O9, (x = 0.0, 0.3, 0.6, and 0.9) sintered pellets synthesized by solid-state reaction method. The as-synthesized samples were analyzed using X-ray diffraction (XRD) and impedance spectroscopy. The emergence of orthorhombic phase fit into space group Pnmm was revealed by XRD, and the addition of Ca resulted in a considerable shift in grain size. Dielectric properties were determined using an impedance spectroscopy in a wide frequency range from 1MHz to 3 GHz. The dielectric properties i.e., dielectric constant (εr) and dielectric loss (tanσ), were measured at 3 GHz frequency. The frequency-dependent parameters such as conductivity, dielectric constant, and dielectric loss indicated that the relaxation process is a Maxwell-Wagner type of interfacial polarization. The improved dielectric properties and low energy loss have made (Ba1-xCax)Ti4O9 a prominent energy storage material. This study provides the possibility to improve its dielectric properties and reduce energy loss, making it an excellent energy storage material.

The Prevailing Preference for Left Nephrectomy in Living Donor Transplantation Does Not Adversely Affect Long-Term Donor and Recipient Outcomes.

BACKGROUND: In living donor renal transplantation, surgeons traditionally prefer the left kidney for donation. The aim of this study was to assess the effects of the choice of laterality of donor nephrectomy on donor and recipient outcomes. METHODS: The data was obtained from the UK National Health Service Blood and Transplant (NHSBT). During the study period, 7919 donor nephrectomy and transplantation were carried out in 24 transplant centers. Of these procedures, 6407 (80.9%) were left and 1512 (19.1%) were right kidney donors. RESULTS: Right kidney donation was associated with higher incidence of surgical site infection in the donor. Recipient outcome was superior for left-sided kidneys in terms of immediate graft function, delayed graft function, graft loss within 30 days, and graft survival at 3 years, but not at 1 and 5 years. Open donor nephrectomy (n = 2396, 30.2%) was associated with higher rates of pneumothorax and hemorrhage, longer hospital stay, and inferior graft survival at 3 and 5 years compared with laparoscopic donor nephrectomy (n = 5523, 69.8%). CONCLUSIONS: A right donor nephrectomy is associated with higher rate of wound infection in the donor and similar long-term graft outcomes in the recipients. Laparoscopic donor nephrectomy offers lower rate of major complications in the donor and a better overall graft survival.

A 24-generation-old founder mutation impairs splicing of RBBP8 in Pakistani families affected with Jawad syndrome.

Jawad syndrome is a multiple congenital anomaly and intellectual disability syndrome with mutation in RBBP8 reported only in two families. Here, we report on two new families from Pakistan and identified a previously reported variant in RBBP8, NM_002894.3:c.1808-1809delTA. We could show that this mutation impairs splicing resulting in two different abnormal transcripts. Finally, we could verify a shared haplotype among all four families and estimate the founder event to have occurred some 24 generations ago.

Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies.

PURPOSE: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition. METHODS: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable. RESULTS: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were predicted to induce premature protein truncation leading to a loss of PCDHGC4 function. The three detected missense variants were located in extracellular cadherin (EC) domains EC5 and EC6 of PCDHGC4, and in silico analysis of the affected residues showed that two of these substitutions were predicted to influence the Ca2+-binding affinity, which is essential for multimerization of the protein, whereas the third missense variant directly influenced the cis-dimerization interface of PCDHGC4. CONCLUSION: We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans.

Modifier Genes in Microcephaly: A Report on WDR62, CEP63, RAD50 and PCNT Variants Exacerbating Disease Caused by Biallelic Mutations of ASPM and CENPJ.

Congenital microcephaly is the clinical presentation of significantly reduced head circumference at birth. It manifests as both non-syndromic-microcephaly primary hereditary (MCPH)-and syndromic forms and shows considerable inter- and intrafamilial variability. It has been hypothesized that additional genetic variants may be responsible for this variability, but data are sparse. We have conducted deep phenotyping and genotyping of five Pakistani multiplex families with either MCPH (n = 3) or Seckel syndrome (n = 2). In addition to homozygous causal variants in ASPM or CENPJ, we discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT-genes already known to be associated with neurological disorders. MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features. Likewise, the phenotype of Seckel syndrome caused by a novel CENPJ variant was aggravated to microcephalic osteodysplastic primordial dwarfism type II (MOPDII) in conjunction with an additional PCNT variant. We show that the CENPJ missense variant impairs splicing and decreases protein expression. We also observed centrosome amplification errors in patient cells, which were twofold higher in MOPDII as compared to Seckel cells. Taken together, these observations advocate for consideration of additional variants in related genes for their role in modifying the expressivity of the phenotype and need to be considered in genetic counseling and risk assessment.

Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia.

PURPOSE: The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a C2H2 domain-containing transcription factor. METHODS: Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform. We performed in-depth clinical phenotyping in all affected individuals. RESULTS: We identified seven affected females in four pedigrees with likely pathogenic variants in ZNF142 that segregate with recessive disease. Affected cases in three families harbor either nonsense or frameshifting likely pathogenic variants predicted to undergo nonsense mediated decay. One additional trio bears ultrarare missense variants in conserved regions of ZNF142 that are predicted to be damaging to protein function. We performed clinical comparisons across our cohort and noted consistent presence of intellectual disability and speech impairment, with variable manifestation of seizures, tremor, and dystonia. CONCLUSION: Our aggregate data support a role for ZNF142 in nervous system development and add to the emergent list of zinc finger proteins that contribute to neurocognitive disorders.

DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer.

Breast cancer is one of the most common malignancies in women worldwide. In breast cancer, the cell proliferation rate is known to influence the cancer malignancy. Recent studies have shown that DNA replication initiation/licensing factors are involved in cancer cell proliferation as well as cancer cell migration and invasion. Licensing factors have also been reported as important prognostic markers in lung, prostrate, and bladder cancers. Here, we studied the role of MCM10, a novel licensing factor, in breast cancer progression. From the public database, NCBI, we investigated six independent breast cancer patient cohorts, totaling 1283 patients. We observed a significant association between high MCM10 mRNA expression with tumor grading and patients' survival time. Most importantly, using breast cancer cohorts with available treatment information, we also demonstrated that a high level of MCM10 is associated with a better response to conventional treatment. Similarly, in in vitro studies, the expression level of MCM10 in breast cancer cell lines is significantly higher compared to paired normal breast epithelium cells. Knockdown of MCM10 expression in the cancer cell line showed significantly decreased tumorigenic properties such as cell proliferation, migration and anchorage independence. The MCF7 breast cancer cell line, after MCM10 expression knockdown, showed significantly decreased tumorigenic properties such as cell proliferation, migration, and anchorage independent growth. Mechanistically, MCM10 expression is observed to be regulated by an Estrogen Receptor (ER) signaling pathway, where its expression is suppressed by the inhibition of the ER or serum withdrawal. Our results suggest that MCM10 plays an important role in breast cancer progression and is a potential prognostic/predictive biomarker and therapeutic target for breast cancer patients.

Renal transplant from infant and neonatal donors is a feasible option for the treatment of end-stage renal disease but is associated with increased early graft loss.

Kidney transplants from young pediatric donors are uncommonly performed in the UK. Published literature of kidney transplant from donors weighing less than 5 kg is sparse. We present our initial experience of en bloc kidney transplantation (EKT) from donors weighing less than 20 kg, including neonatal donors. All recipients undergoing EKT from donors under 20 kg at our center from January 2005 to October 2016 were included. Donor and recipient details were recorded from a prospective database. Electronic patient records were examined for follow-up data. Of 30 EKTs included, 15 were from ≤5 kg donors and 15 from >5 kg donors (median weight 3.4 and 12.7 kg, respectively). One-year graft survival for ≤5 kg and >5 kg donors for EKT was 86.7% and 93.3% (P = 0.85), respectively. Progressive improvement in estimated GFR (eGFR) was noted in both donor categories through first-year posttransplant but in the ≤5 kg donor category significant improvement was seen at 12 months compared to 3 months after transplantation (median eGFR 37.3 vs 70.0 mL/min/1.73 m2 , P = 0.03). Two early graft losses were attributable to early vascular complications and one graft loss due to primary nonfunction. Our data show that kidney transplantation from such donors is a feasible option at centers with experience of EKT, albeit with increased risk of early graft loss.