Clinical characteristics, management, outcome, and cost of stings and bites in patients admitted to a tertiary care teaching hospital.

AIM: The objective of this study was to identify the clinical epidemiology and medical cost of stings and bites at a tertiary care hospital in South India. SUBJECTS AND METHODS: The medical records of hospitalized patients in the tertiary care unit between 2016 and 2020 with the history of either being stung or bitten by insects were reviewed retrospectively. The patient's demographic details, clinical symptoms, treatment chart, expenditure details, and outcomes were collected in pre-structured case report forms. The data were analyzed using SPSS Version 20.0. RESULTS: A total of 66 patients were enrolled, with a mean age of 45.86 ± 23.37 years. The majority of the incidence was due to bee stings (61%). Anaphylaxis was reported in 38% of the cases, followed by acute kidney injury (10.6%). The cost of hospitalization was found to be higher for spider bites at 896.73 ± 1414.95 USD, followed by wasp stings at 989.81 ± 1185.57 USD. In patients with complications, the average cost of stings and bites was 438.81 ± 685.81 USD. Most of the patients received antibiotics (75.8%), followed by steroids (62.1%). CONCLUSION: Stings and bite injuries may appear harmless initially, but they can cause severe complications in unidentified cases and for those who do not seek urgent medical attention. Antibiotics and corticosteroids can help in the management of envenomation.

Electronic Structure Engineered Heteroatom Doped All Transition Metal Sulfide Carbon Confined Heterostructure for Extrinsic Pseudocapacitor.

Ultra-high energy density battery-type materials are promising candidates for supercapacitors (SCs); however, slow ion kinetics and significant volume expansion remain major barriers to their practical applications. To address these issues, hierarchical lattice distorted α-/γ-MnS@Cox Sy core-shell heterostructure constrained in the sulphur (S), nitrogen (N) co-doped carbon (C) metal-organic frameworks (MOFs) derived nanosheets (α-/γ-MnS@Cox Sy @N, SC) have been developed. The coordination bonding among Cox Sy , and α-/γ-MnS nanoparticles at the interfaces and the π-π stacking interactions developed across α-/γ-MnS@Cox Sy and N, SC restrict volume expansion during cycling. Furthermore, the porous lattice distorted heteroatom-enriched nanosheets contain a sufficient number of active sites to allow for efficient electron transportation. Density functional theory (DFT) confirms the significant change in electronic states caused by heteroatom doping and the formation of core-shell structures, which provide more accessible species with excellent interlayer and interparticle conductivity, resulting in increased electrical conductivity. . The α-/γ-MnS@Cox Sy @N, SC electrode exhibits an excellent specific capacity of 277 mA hg-1 and cycling stability over 23 600 cycles. A quasi-solid-state flexible extrinsic pseudocapacitor (QFEPs) assembled using layer-by-layer deposited multi-walled carbon nanotube/Ti3 C2 TX nanocomposite negative electrode. QFEPs deliver specific energy of 64.8 Wh kg-1 (1.62 mWh cm-3 ) at a power of 933 W kg-1 and 92% capacitance retention over 5000 cycles.

Reconfiguring the Electronic Structure of Heteroatom Doped Carbon Supported Bimetallic Oxide@Metal Sulfide Core-Shell Heterostructure via In Situ Nb Incorporation toward Extrinsic Pseudocapacitor.

High-energy-density battery-type materials have sparked considerable interest as supercapacitors electrode; however, their sluggish charge kinetics limits utilization of redox-active sites, resulting in poor electrochemical performance. Here, the unique core-shell architecture of metal organic framework derived N-S codoped carbon@Cox Sy micropetals decorated with Nb-incorporated cobalt molybdate nanosheets (Nb-CMO4 @Cx Sy NC) is demonstrated. Coordination bonding across interfaces and π-π stacking interactions between CMO4 @Cx Sy and N and, S-C can prevent volume expansion during cycling. Density functional theory analysis reveals that the excellent interlayer and the interparticle conductivity imparted by Nb doping in heteroatoms synergistically alter the electronic states and offer more accessible species, leading to increased electrical conductivity with lower band gaps. Consequently, the optimized electrode has a high specific capacity of 276.3 mAh g-1 at 1 A g-1 and retains 98.7% of its capacity after 10 000 charge-discharge cycles. A flexible quasi-solid-state SC with a layer-by-layer deposited reduced graphene oxide /Ti3 C2 TX anode achieves a specific energy of 75.5 Wh kg-1 (volumetric energy of 1.58 mWh cm-3 ) at a specific power of 1.875 kWh kg-1 with 96.2% capacity retention over 10 000 charge-discharge cycles.

Genomic Analysis of AZD1222 (ChAdOx1) Vaccine Breakthrough Infections in the City of Mumbai.

Background: This manuscript describes the genetic features of SARS-CoV-2 mutations, prevalent phylogenetic lineages, and the disease severity amongst COVID-19-vaccinated individuals in a tertiary cancer hospital during the second wave of the pandemic in Mumbai, India. Methods: This observational study included 159 COVID-19 patients during the second wave of the pandemic from 17th March to 1st June 2021 at a tertiary cancer care centre in Mumbai. The cohort comprised of healthcare workers, staff relatives, cancer patients, and patient relatives. For comparison, 700 SARS-CoV-2 genomes sequenced during the first wave (23rd April to 25th September 2020) at the same centre were also analysed. Patients were assigned to nonvaccinated (no vaccination or <14 days from the 1st dose, n = 92), dose 1(≥14 days from the 1st dose to <14 days from the 2nd dose, n = 29), and dose 2 (≥14 days from the 2nd dose, n = 38) groups. Primary measure was the prevalence of SARS-CoV-2 genomic lineages among different groups. In addition, severity of COVID-19 was assessed according to clinical and genomic variables. Results: Kappa B.1.1671.1 and delta B.1.617.2 variants contributed to an overwhelming majority of sequenced genomes (unvaccinated: 40/92, 43.5% kappa, 46/92, 50% delta; dose 1: 14/29, 48.3% kappa, 15/29, 51.7% delta; and dose 2: 23/38, 60.5% kappa, 14/38 36.8% delta). The proportion of the kappa and delta variants did not differ significantly across the unvaccinated, dose 1, and dose 2 groups (p = 0.27). There was no occurrence of severe COVID-19 in the dose 2 group (0/38, 0% vs. 14/121, 11.6%; p = 0.02). SARS-CoV-2 genomes from all three severe COVID-19 patients in the vaccinated group belonged to the delta lineage (3/28, 10.7% vs. 0/39, 0.0%, p = 0.04). Conclusions: Sequencing analysis of SARS-COV-2 genomes from Mumbai during the second wave of COVID-19 suggests the prevalence of the kappa B.1.617.1 and the delta B.1.627.2 variants among both vaccinated and unvaccinated individuals. Continued evaluation of genomic sequencing data from breakthrough COVID-19 is necessary for monitoring the properties of evolving variants of concern and formulating appropriate immune response boosting and therapeutic strategies.

SARS-CoV-2 reinfection after previous infection and vaccine breakthrough infection through the second wave of pandemic in India: An observational study.

BACKGROUND: There are sparse longitudinal data on SARS-CoV-2 infection after previous infection and after partial or full vaccination. METHODS: This study of a cohort of healthcare workers used Kaplan-Meier analysis with appropriate definition of events and censoring and used Cox models to assess outcomes, with data cut-off on June 18, 2021. RESULTS: A total of 1806 individuals with median age of 32 (18-64) years, 1483 (82.1%) with at least one vaccine dose, 1085 (60.1%) with 2 vaccine doses, 408 (22.6%) with at least one episode of SARS-CoV-2 infection, and 6 (1.47%) with 2 episodes of infection were included in the analysis. At median follow-up of 38.4 weeks after first SARS-CoV-2 infection (n=408), the 52-week probability of reinfection was 2.2% (95% CI, 1.0-4.91%); and at median follow-up of 13.3 weeks after second dose, the 16-week probability of breakthrough infection was 5.6% (95% CI, 4.33-7.23%), which was significantly higher among those without previous SARS-CoV-2 infection versus with previous infection (6.4% vs 1.8%, p=0.016, adjusted Cox HR=3.49, 95% CI, 1.09-11.20, p=0.036) and females versus males (7.9% vs 3.8%, p=0.007, adjusted Cox HR=2.06, 95% CI 1.19-3.56, p=0.01). CONCLUSIONS: There was low probability of reinfection after previous SARS-CoV-2 infection and higher vaccine breakthrough infections among females and those without previous infection.

Clinical characteristics, laboratory parameters and outcomes of COVID-19 in cancer and non-cancer patients from a tertiary Cancer Centre in India.

BACKGROUND: There is paucity of data regarding clinical characteristics, laboratory parameters and outcomes of coronavirus disease (COVID-19) in cancer versus non-cancer patients, particularly from India. MATERIALS AND METHODS: This was an observational, single-centre, retrospective analysis of patients with laboratory-confirmed COVID-19 hospitalised in our institution between 22 May 2020 and 1 December 2020. We compared baseline clinical characteristics, laboratory parameters and outcomes of COVID-19 (overall mortality, time to discharge) between cancer and non-cancer patients. RESULTS: A total of 200 COVID-19 infection episodes were analysed of which 109 (54.5%) were patients with cancer and 91 (45.5%) were patients without cancer. The median age was 43 (interquartile range [IQR]:32-57), 51 (IQR: 33-62) and 38 (IQR: 31.5-49.3) years; of whole cohort, cancer and non-cancer patients, respectively. Comparison of outcomes showed that oxygen requirement (31.2% [95% CI: 22.6-40.7] vs. 17.6% [95% CI: 10.4-26.9]; p = 0.03), median time to discharge (11 days [IQR: 6.75-16] vs. 6 days [IQR: 3-9.75]; p < 0.001) and mortality (10.0% [95% CI: 5.2-17.3] vs. 1.1% [95% CI: 0.03-5.9]; p = 0.017) were significantly higher in patients with cancer. In univariable analysis, factors associated with higher mortality in the whole cohort included diagnosis of cancer (10.1% vs. 1.1%; p = 0.027; odds ratio [OR]: 7.04), age ≥60 (17.4% vs. 2.6%; p = 0.001; OR: 7.38), oxygen requirement (22% vs. 0.6%; p < 0.001; OR: 29.01), chest infiltrates (19.2% vs. 1.4%; p < 0.001; OR: 22.65), baseline absolute lymphocyte count <1 × 109 /L (10.8% vs. 1.9%; p = 0.023; OR:5.1), C-reactive protein >1 mg% (12.8% vs. 0%; p = 0.027; OR: 24.69), serum procalcitonin >0.05 ng/ml (22.65% vs. 0%; p = 0.004; OR: 4.49) and interleukin-6 >6 pg/ml (10.8% vs. 1.3%; p = 0.036; OR: 3.08). In multivariable logistic regression, factors significantly associated with mortality were oxygen requirement (p = 0.005; OR: 13.11) and high baseline procalcitonin level (p = 0.014; OR: 37.6). CONCLUSION: Cancer patients with COVID-19 have higher mortality and require longer hospital stay. High procalcitonin levels and oxygen requirement during admission are other factors that affect outcomes adversely.

Biomass-Derived N-Doped Carbon for Efficient Electrocatalytic CO2 Reduction to CO and Zn-CO2 Batteries.

Conversion of CO2 into valuable chemicals via electrochemical CO2 reduction reaction (CO2RR) is a promising technology to alleviate the energy crisis and the greenhouse effect. Herein, low-cost wood biomass was applied as the carbon source to prepare nitrogen (N)-doped carbon electrocatalysts for the conversion of CO2 to CO and further as the cathode material for Zn-CO2 batteries. By virtue of N-doping and assistance of FeCl3, a cedar biomass-derived three-dimensional (3D) N-doped graphitized carbon with a high N-doping content (5.38%), an ultrahigh specific surface area (1673.6 m2 g-1), rich nanopores, and sufficient active N sites was successfully obtained, which exhibited super CO2RR activity with a high faradaic efficiency of 91% at a low applied potential of 0.56 V (vs RHE) and a long-term stability for at least 20 h. Furthermore, a Zn-CO2 battery with it as the cathode material delivered a stable open circuit voltage of 0.79 V, a peak power density of 0.51 mW cm-2 at 2.14 mA cm-2, and a maximum faradaic efficiency to CO of 80.4% at 2.56 mA cm-2, indicating that it could be applied in a practical process by using CO2 to generate power with the production of CO. Density functional theory calculations revealed that pyridinic N could more effectively decrease the free energy barriers for CO2RR and boost the reaction. This work not only revealed a facile approach to convert waste biomass into N-doped-graphitization carbon as valuable CO2RR electrocatalysts but also provided a new strategy to achieve "carbon solving carbon's problem".

Fabrication of a High-Energy Flexible All-Solid-State Supercapacitor Using Pseudocapacitive 2D-Ti3C2Tx-MXene and Battery-Type Reduced Graphene Oxide/Nickel-Cobalt Bimetal Oxide Electrode Materials.

Owing to excellent metallic conductivity, hydrophilic surfaces, and surface redox properties, a two-dimensional (2D) metal carbide of Ti3C2Tx-MXene could serve as a promising pseudocapacitive electrode material for energy storage devices. Meanwhile, the 2D reduced graphene oxide (rGO) combining with the hierarchical cubic spinel nickel-cobalt bimetal oxide (NiCo2O4) nanospikes could control ion diffusion for charge storage, thereby facilitating the improvement of the energy density of a supercapacitor. As per the strategy, the pseudocapacitive 2D Ti3C2Tx was loaded on a flexible acid-treated carbon fiber (ACF) backbone to prepare a Ti3C2Tx/ACF negative electrode by a convenient drop-casting method. Meanwhile, 2D rGO was deposited on ACF by a simple dip-dry process, which was further decorated by the spinel NiCo2O4 nanospikes using a hydrothermal method to obtain a NiCo2O4@rGO/ACF positive electrode. The fabricated Ti3C2Tx/ACF electrode exhibited an excellent specific capacitance of 246.9 F/g (197.5 mF/cm2) at 4 mA/cm2 along with 96.7% capacity retention over 5000 charge/discharge cycles, whereas the NiCo2O4@rGO/ACF electrode showed a specific capacitance of 1487 F/g (458.3 mA h/g) at 3 mA/cm2 with a cycling stability of 88.2% over 10 000 charge/discharge cycles. As a result, a flexible all-solid-state hybrid supercapacitor (FHSC) device using the pseudocapacitive Ti3C2Tx/ACF on the negative side with a widespread voltage window and the battery-type NiCo2O4@rGO/ACF on the positive side with high electrochemical activity delivered an excellent volumetric capacitance of 2.32 F/cm3 (141.9 F/g) at a current density of 5 mA/cm2 with a high-energy density of 44.36 Wh/kg (0.72 mWh/cm3) at a power density of 985 W/kg (16.13 mW/cm3) along with a cycling stability of 90.48% over 4500 charge/discharge cycles. Therefore, the pseudocapacitive 2D Ti3C2Tx/ACF negative electrode could replace carbon-based electrodes and a combination of it with the battery-type NiCo2O4@rGO/ACF positive electrode should be a promising way to step up the energy density of a supercapacitor.

Strategic consideration for effective chemotherapeutic transportation via transpapillary route in breast cancer.

Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. The current treatment option for breast cancer includes drug treatment (Chemotherapy and hormone therapy) or surgery (mastectomy and lumpectomy). The major drawbacks of chemotherapy include rapid metabolism, limited ductal exposure, lower bioavailability, higher elimination rate, undesirable side effects, and high dose of drug. Localized application of drug to breast achieves higher drug levels at the tumor site and reduces systemic drug distribution. Permeation of drug by local application is mainly by transepidermal and transductal routes. The multiple duct openings of mammary papilla provide a higher permeable surface for transport of drug. Various formulation approaches like conjugated nanocarriers, microemulsion, nanoemulsion, liposomes, microneedles and iontophoresis are used to achieve a tailored and targeted drug delivery to underlying breast tissue. Localized transport of drug via transpapillary route has developed a novel and effective non-invasive drug delivery approach to achieve a systemic drug level at the tumor site in the management of breast cancer.

Enhancing the one health initiative by using whole genome sequencing to monitor antimicrobial resistance of animal pathogens: Vet-LIRN collaborative project with veterinary diagnostic laboratories in United States and Canada.

BACKGROUND: Antimicrobial resistance (AMR) of bacterial pathogens is an emerging public health threat. This threat extends to pets as it also compromises our ability to treat their infections. Surveillance programs in the United States have traditionally focused on collecting data from food animals, foods, and people. The Veterinary Laboratory Investigation and Response Network (Vet-LIRN), a national network of 45 veterinary diagnostic laboratories, tested the antimicrobial susceptibility of clinically relevant bacterial isolates from animals, with companion animal species represented for the first time in a monitoring program. During 2017, we systematically collected and tested 1968 isolates. To identify genetic determinants associated with AMR and the potential genetic relatedness of animal and human strains, whole genome sequencing (WGS) was performed on 192 isolates: 69 Salmonella enterica (all animal sources), 63 Escherichia coli (dogs), and 60 Staphylococcus pseudintermedius (dogs). RESULTS: We found that most Salmonella isolates (46/69, 67%) had no known resistance genes. Several isolates from both food and companion animals, however, showed genetic relatedness to isolates from humans. For pathogenic E. coli, no resistance genes were identified in 60% (38/63) of the isolates. Diverse resistance patterns were observed, and one of the isolates had predicted resistance to fluoroquinolones and cephalosporins, important antibiotics in human and veterinary medicine. For S. pseudintermedius, we observed a bimodal distribution of resistance genes, with some isolates having a diverse array of resistance mechanisms, including the mecA gene (19/60, 32%). CONCLUSION: The findings from this study highlight the critical importance of veterinary diagnostic laboratory data as part of any national antimicrobial resistance surveillance program. The finding of some highly resistant bacteria from companion animals, and the observation of isolates related to those isolated from humans demonstrates the public health significance of incorporating companion animal data into surveillance systems. Vet-LIRN will continue to build the infrastructure to collect the data necessary to perform surveillance of resistant bacteria as part of fulfilling its mission to advance human and animal health. A One Health approach to AMR surveillance programs is crucial and must include data from humans, animals, and environmental sources to be effective.

Flexible Asymmetric Solid-State Supercapacitors by Highly Efficient 3D Nanostructured α-MnO2 and h-CuS Electrodes.

A simplistic and economical chemical way has been used to prepare highly efficient nanostructured, manganese oxide (α-MnO2) and hexagonal copper sulfide (h-CuS) electrodes directly on cheap and flexible stainless steel sheets. Flexible solid-state α-MnO2/flexible stainless steel (FSS)/polyvinyl alcohol (PVA)-LiClO4/h-CuS/FSS asymmetric supercapacitor (ASC) devices have been fabricated using PVA-LiClO4 gel electrolyte. Highly active surface areas of α-MnO2 (75 m2 g-1) and h-CuS (83 m2 g-1) electrodes contribute to more electrochemical reactions at the electrode and electrolyte interface. The ASC device has a prolonged working potential of +1.8 V and accomplishes a capacitance of 109.12 F g-1 at 5 mV s-1, energy density of 18.9 Wh kg-1, and long-term electrochemical cycling with a capacity retention of 93.3% after 5000 cycles. Additionally, ASC devices were successful in glowing seven white-light-emitting diodes for more than 7 min after 30 s of charging. Outstandingly, real practical demonstration suggests "ready-to-sell" products for industries.

An innovative concept of use of redox-active electrolyte in asymmetric capacitor based on MWCNTs/MnO2 and Fe2O3 thin films.

In present investigation, we have prepared a nanocomposites of highly porous MnO2 spongy balls and multi-walled carbon nanotubes (MWCNTs) in thin film form and tested in novel redox-active electrolyte (K3[Fe(CN)6] doped aqueous Na2SO4) for supercapacitor application. Briefly, MWCNTs were deposited on stainless steel substrate by "dip and dry" method followed by electrodeposition of MnO2 spongy balls. Further, the supercapacitive properties of these hybrid thin films were evaluated in hybrid electrolyte ((K3[Fe(CN)6 doped aqueous Na2SO4). Thus, this is the first proof-of-design where redox-active electrolyte is applied to MWCNTs/MnO2 hybrid thin films. Impressively, the MWCNTs/MnO2 hybrid film showed a significant improvement in electrochemical performance with maximum specific capacitance of 1012 Fg-1 at 2 mA cm-2 current density in redox-active electrolyte, which is 1.5-fold higher than that of conventional electrolyte (Na2SO4). Further, asymmetric capacitor based on MWCNTs/MnO2 hybrid film as positive and Fe2O3 thin film as negative electrode was fabricated and tested in redox-active electrolytes. Strikingly, MWCNTs/MnO2//Fe2O3 asymmetric cell showed an excellent supercapacitive performance with maximum specific capacitance of 226 Fg-1 and specific energy of 54.39 Wh kg-1 at specific power of 667 Wkg-1. Strikingly, actual practical demonstration shows lightning of 567 red LEDs suggesting "ready-to sell" product for industries.

Degradation of imidacloprid containing wastewaters using ultrasound based treatment strategies.

The present work deals with application of sonochemical reactors for the treatment of imidacloprid containing wastewaters either individually or in combination with other advanced oxidation processes. Experiments have been performed using two different configurations of sonochemical reactors viz. ultrasonic horn (20 kHz frequency and rated power of 240 W) and ultrasonic bath equipped with radially vibrating horn (25 kHz frequency and 1 kW rated power). The work also investigates the effect of addition of process intensifying agents such as H2O2 and CuO, which can enhance the production of free radicals in the system. The combination studies with advanced oxidation process involve the advanced Fenton process and combination of ultrasound with UV based oxidation. The extent of degradation obtained using combination of US and H2O2 at optimum loading of H2O2 was found to be 92.7% whereas 96.5% degradation of imidacloprid was achieved using the combination of US and advanced Fenton process. The process involving the combination of US, UV and H2O2 was found to be the best treatment approach where complete degradation of imidacloprid was obtained with 79% TOC removal. It has been established that the use of cavitation in combination with different oxidation processes can be effectively used for the treatment of imidacloprid containing wastewater.

Rattusin, an intestinal α-defensin-related peptide in rats with a unique cysteine spacing pattern and salt-insensitive antibacterial activities.

Cationic antimicrobial peptides are essential components of the innate immune system. As a major family of mammalian antimicrobial peptides, defensins are expressed mainly by mucosal epithelial cells and promyelocytes. Despite the capacity to kill a broad spectrum of bacteria through physical disruption of membranes, most defensins show substantially reduced antibacterial activities in the presence of monovalent and divalent cations, thereby limiting their therapeutic potential, particularly for the treatment of systemic infections. Genome-wide computational screening of the rat genome led to the identification of the gene for a novel α-defensin-related peptide that we termed rattusin. Rattusin shares a highly conserved signal and prosequence with mammalian α-defensins, but instead of the canonical α-defensin six-cysteine motif, rattusin consists of five cysteines with a distinctive spacing pattern. Furthermore, rattusin is preferentially expressed in Paneth cells of the distal small intestine with potent antibacterial activity against a broad range of Gram-negative and Gram-positive bacteria, including antibiotic-resistant strains. The MICs were mostly in the range of 2 to 4 µM, with no appreciable toxicity to mammalian cells at up to 100 µM. In contrast to classical α- and ß-defensins, rattusin retained its activity in the presence of physiological concentrations of NaCl and Mg(2+), making it an attractive antimicrobial candidate for both topical and systemic applications.

Bioinformatic and expression analysis of novel porcine beta-defensins.

Beta-defensins are a major group of mammalian antimicrobial peptides. Although more than 30 beta-defensins have been identified in humans, only one porcine beta-defensin has been reported. In this article we report the identification and initial characterization of 11 novel porcine beta-defensins (pBD). Using bioinformatic approaches, we screened 287,821 porcine expressed sequence tags for similarity of their predicted peptides to known human beta-defensins and identified full-length or partial sequences for the 11 novel pBDs. Similar to the previously identified pBD1, all of these peptides have a consensus beta-defensin motif. A differential expression pattern for these newly identified genes was found. For example, unlike most beta-defensins, pBD2 and pBD3 were expressed in bone marrow and in other lymphoid tissues including thymus, spleen, lymph nodes, duodenum, and liver. Including pBD2 and pBD3, six porcine beta-defensins were expressed in lung and skin. Several newly identified porcine beta-defensins, including pBD123, pBD125, and pBD129, were expressed in male reproductive tissues, including lobuli testis and some segments of the epididymis. Phylogenetic analysis indicates that in most cases the evolutionary relationship between individual porcine beta-defensins and their human orthologs is closer than the relationship among beta-defensins in the same species. These findings establish the existence of multiple porcine beta-defensins and suggest that the pig may be an ideal model for the characterization of beta-defensin diversity and function.

Cross-species analysis of the mammalian beta-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract.

Mammalian beta-defensins are an important family of innate host defense peptides with pleiotropic activities. As a first step to study the evolutionary relationship and biological role of the beta-defensin family, we identified their complete repertoires in the human, chimpanzee, mouse, rat, and dog following systemic, genome-wide computational searches. Although most beta-defensin genes are composed of two exons separated by an intron of variable length, some contain an additional one or two exons encoding an internal pro-sequence, a segment of carboxy-terminal mature sequences or untranslated regions. Alternatively, spliced isoforms have also been found with several beta-defensins. Furthermore, all beta-defensin genes are densely clustered in four to five syntenic chromosomal regions, with each cluster spanning <1.2 Mb across the five species. Phylogenetic analysis indicated that, although the majority of beta-defensins are evolutionarily conserved across species, subgroups of gene lineages exist that are specific in certain species, implying that some beta-defensins originated after divergence of these mammals from each other, while most others arose before the last common ancestor of mammals. Surprisingly, RT-PCR revealed that all but one rat beta-defensin transcript are preferentially expressed in the male reproductive tract, particularly in epididymis and testis, except that Defb4, a human beta-defensin-2 ortholog, is more restricted to the respiratory and upper gastrointestinal tracts. Moreover, most beta-defensins expressed in the reproductive tract are developmentally regulated, with enhanced expression during sexual maturation. Existence of such a vast array of beta-defensins in the male reproductive tract suggests that these genes may play a dual role in both fertility and host defense.

Rapid evolution and diversification of mammalian alpha-defensins as revealed by comparative analysis of rodent and primate genes.

Mammalian alpha-defensins constitute a family of cysteine-rich, cationic antimicrobial peptides produced by phagocytes and intestinal Paneth cells, playing an important role in innate host defense. Following comprehensive computational searches, here we report the discovery of complete repertoires of the alpha-defensin gene family in the human, chimpanzee, rat, and mouse with new genes identified in each species. The human genome was found to encode a cluster of 10 distinct alpha-defensin genes and pseudogenes expanding 132 kb continuously on chromosome 8p23. Such alpha-defensin loci are also conserved in the syntenic chromosomal regions of chimpanzee, rat, and mouse. Phylogenetic analyses showed formation of two distinct clusters with primate alpha-defensins forming one cluster and rodent enteric alpha-defensins forming the other cluster. Species-specific clustering of genes is evident in nonprimate species but not in the primates. Phylogenetically distinct subsets of alpha-defensins also exist in each species, with most subsets containing multiple members. In addition, natural selection appears to have acted to diversify the functionally active mature defensin region but not signal or prosegment sequences. We concluded that mammalian alpha-defensin genes may have evolved from two separate ancestors originated from beta-defensins. The current repertoires of the alpha-defensin gene family in each species are primarily a result of repeated gene duplication and positive diversifying selection after divergence of mammalian species from each other, except for the primate genes, which were evolved prior to the separation of the primate species. We argue that the presence of multiple, divergent subsets of alpha-defensins in each species may help animals to better cope with different microbial challenges in the ecological niches which they inhabit.