Non B Cell-Derived Immunoglobulin, A Brighter Horizon for the Future.

The canonical theory of immunology stating that "Immunoglobulin (Ig) is produced by B lymphocytes and exerts antibody activity" has been established since the 1970s. However, the discovery of non B cell-derived Igs (non B-Igs), which can exert multiple biological activities in addition to their antibody activities, necessitates a reevaluation of the classic concept of Ig. This has been documented with a number of characteristics related to their structure, modification, genetic regulation as well as the functions associated with clinical conditions, particularly multiple cancers. The discovery of non B-Ig provides us with a new perspective to better understand not only basic immunology, but also various Ig-related clinical manifestations including autoimmune diseases, chronic inflammation, and anaphylaxis. Notably, non B-Ig can directly promote the occurrence of malignant tumours.

Origin and maintenance of large ribosomal RNA gene repeat size in mammals.

The genes encoding ribosomal RNA are highly conserved across life and in almost all eukaryotes are present in large tandem repeat arrays called the rDNA. rDNA repeat unit size is conserved across most eukaryotes, but has expanded dramatically in mammals, principally through expansion of the intergenic spacer region that separates adjacent rRNA coding regions. Here we used long-read sequence data from representatives of the major amniote lineages to determine where in amniote evolution rDNA unit size increased. We find that amniote rDNA unit sizes fall into two narrow size classes: 'normal' (∼11-20 kb) in all amniotes except monotreme, marsupial and eutherian mammals, which have 'large' (∼35-45 kb) sizes. We confirm that increases in intergenic spacer length explain much of this mammalian size increase but, in stark contrast to the uniformity of mammalian rDNA unit size, mammalian intergenic spacers differ greatly in sequence. These results suggest a large increase in intergenic spacer size occurred in a mammalian ancestor and has been maintained despite substantial sequence changes over the course of mammalian evolution. This points to a previously unrecognized constraint on the length of the intergenic spacer, a region that was thought to be largely neutral. We finish by speculating on possible causes of this constraint.

Patients with STAT1 Gain-of-function Mutations Display Increased Apoptosis which is Reversed by the JAK Inhibitor Ruxolitinib.

INTRODUCTION: The signal transducer and activator of transcription (STAT1) gain-of-function (GOF) syndrome accounts for most cases of chronic mucocutaneous candidiasis but is characterized by a broader clinical phenotype that may include bacterial, viral, or invasive fungal infections, autoimmunity, autoinflammatory manifestations, vascular complications, or malignancies. The severity of lymphopenia may vary and influence the infectious morbidity. METHODS: In our cohort of seven STAT1-GOF patients, we investigated the mechanisms that may determine T lymphopenia, we characterized the interferon gene signature (IGS) and analyzed the effect of ruxolitinib in reverting the immune dysregulation. RESULTS: STAT1-GOF patients exhibited increased T lymphocyte apoptosis that was significantly augmented in both resting conditions and following stimulation with mitogens and IFNα, as evaluated by flow cytometry by Annexin V/ Propidium iodide assay. The JAK inhibitor ruxolitinib significantly reduced the IFNα-induced hyperphosphorylation of STAT1 and reverted the stimulation-induced T-cell apoptosis, in vitro. In two adult STAT1-GOF patients, the JAKinib treatment ameliorated chronic mucocutaneous candidiasis and lymphopenia. Most STAT1-GOF patients, particularly those who had autoimmunity, presented increased IGS that significantly decreased in the two patients during ruxolitinib treatment. CONCLUSION: In STAT1-GOF patients, T lymphocyte apoptosis is increased, and T lymphopenia may determine higher risk of severe infections. The JAKinib target therapy should be evaluated to treat severe chronic candidiasis and lymphopenia, and to downregulate the IFNs in patients with autoinflammatory or autoimmune manifestations.

Casein kinase 1 inhibitor avoids TDP-43 pathology propagation in a patient-derived cellular model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease without a cure to reverse its progression. Its main hallmark is the nuclear protein TDP-43, which undergoes different post-translational modifications leading to a loss of function in the nucleus and an increase in toxicity in the cytoplasm. Previous reports have indicated that pathogenic TDP-43 exhibits prion-like propagation in various contexts. With the aim of advancing therapeutics focused on preventing the propagation of TDP-43 pathology, we studied the potential role of pathogenic TDP-43 in lymphoblasts from sporadic ALS patients. We used lymphoblastoid cell lines from sporadic ALS patients as a source of pathogenic forms of TDP-43, and healthy human cells (lymphoblasts, myoblasts, neuroblastoma SH-SY5Y, or osteosarcoma U2OS) as recipient cells to investigate the seeding and spread of TDP-43 proteinopathy. Furthermore, we evaluated the potential of targeting TDP-43 phosphorylation with a CK-1 inhibitor to prevent the propagation of the pathology. The results presented herein indicate that pathogenic forms of TDP-43 are secreted into the extracellular medium of sporadic ALS lymphoblasts and could be transported by extracellular vesicles, spreading TDP-43 pathology to healthy cells. Moreover, tunneling nanotubes have also been discovered in pathological cells and may be involved in the transport of TDP-43. Interestingly, targeting TDP-43 phosphorylation with an in-house designed CK-1 inhibitor (IGS2.7) was sufficient to halt TDP-43 pathology transmission, in addition to its known effects on restoring the homeostasis of TDP-43 protein in patients-derived cells.

Circulating T follicular helper 2 cells, T follicular regulatory cells and regulatory B cells are effective biomarkers for predicting the response to house dust mite sublingual immunotherapy in patients with allergic respiratory diseases.

The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. Der-p/f sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and Der-p/f sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4+ cTfh cells were significantly decreased and the percentage of IFN-γ+ cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR.

The Implementation of Precise Point Positioning (PPP): A Comprehensive Review.

High-precision positioning from Global Navigation Satellite Systems (GNSS) has garnered increased interest due to growing demand in various applications, like autonomous car navigation and precision agriculture. Precise Point Positioning (PPP) offers a distinct advantage over differential techniques by enabling precise position determination of a GNSS rover receiver through the use of external corrections sourced from either the Internet or dedicated correction satellites. However, PPP's implementation has been challenging due to the need to mitigate numerous GNSS error sources, many of which are eliminated in differential techniques such as Real-Time Kinematics (RTK) or overlooked in Standard Point Positioning (SPP). This paper extensively reviews PPP's error sources, such as ionospheric delays, tropospheric delays, satellite orbit and clock errors, phase and code biases, and site displacement effects. Additionally, this article examines various PPP models and correction sources that can be employed to address these errors. A detailed discussion is provided on implementing the standard dual-frequency (DF)-PPP to achieve centimeter- or millimeter-level positioning accuracy. This paper includes experimental examples of PPP implementation results using static data from the International GNSS Service (IGS) station network and a kinematic road test based on the actual trajectory to showcase DF-PPP development for practical applications. By providing a fusion of theoretical insights with practical demonstrations, this comprehensive review offers readers a pragmatic perspective on the evolving field of Precise Point Positioning.

Humoral immune responses in different stages of wound healing in Black Bengal goats.

Objective: The current study was carried out to assess the humoral immune responses according to age at different stages of wound healing in Black Bengal goats (BBG). Materials and Methods: Apparently, healthy BBGs (n = 20) were collected and divided into five groups based on their age: Group A (control, 3 years), Group B (3 to 5 years), Group C (2 to <3 years), Group D (1 to <2 years), and Group E (<1 year). Except for control, all BBGs were allowed to have artificial surgical wounds, and follow-up data were collected from day 0 to 21. The humoral immune responses [immunoglobulins (Igs) and interleukin-6 (IL-6)] were determined by ELISA using commercial goat ELISA kits. Statistical Product and Service Solutions (Version 20) was used to analyze the data. Results: The normal range of immune cells in control BBGs was immunoglobulin G (IgG) (20.21 ± 0.13 mg/ml), immunoglobulin M (IgM) (2.87 ± 0.0.05 mg/ml), immunoglobulin A (IgA) (0.33 ± 0.01 mg/ml), and IL-6 (1.6 ± 0.05 pg/ml). In this experiment, higher concentrations of IgG (21.11 ± 0.20 mg/ml), IgM (2.92 ± 0.04 mg/ml), IgA (0.35 ± 0.02 mg/ml), and IL-6 (1.62 ± 0.05 pg/ml) were found in Group B BBGs, whereas the lower levels of IgG, IgM, IgA, and IL-6 were found at 17.16 ± 0.18 mg/ml, 2.12 ± 0.01 mg/ml, 0.29 ± 0.03 mg/ml, and 1.55 ± 0.05 pg/ml, respectively, in the Group E BBGs. Rapid wound healing was observed in the older groups compared to the younger groups of BBGs. The concentrations of Igs (IgG, IgM, and IgA) and IL-6 were gradually increased in all groups from day 3 (early inflammatory stage) and day 7 (late inflammatory stage), and then they decreased gradually from day 14 (proliferative stage) to reach the final stage of day 21 (remodeling stage), where the concentrations were found to be at a level comparable to their per-incisional period. No gender-related differences were detected. Conclusion: Adult BBGs (3 to 5 years old) showed faster wound repair and stronger immune responses. This finding may assist veterinarians and researchers in considering age-related immune responses for the recovery and rapid cure of surgical wounds.

Outage Performance Analysis of Improper Gaussian Signaling for Two-User Downlink NOMA Systems with Imperfect Successive Interference Cancellation.

The improper Gaussian signaling (IGS) technique can improve the achievable rate of an interference-limited network by fully exploiting the second-order statistics of complex signaling. This paper addresses the outage performance analysis of a two-user downlink non-orthogonal multiple access (NOMA) system using the IGS technique in the presence of imperfect successive interference cancellation (SIC). The strong channel user (SU) adopts the IGS, while the weak channel user (WU) adopts the traditional proper Gaussian signaling (PGS). Considering a practical scenario where the transmitter has obtained the statistics of the channel coefficients instead of the instantaneous channel state information (CSI), the expressions of the achievable rates of both users under residual interference due to imperfect SIC are derived, together with their outage probabilities, subject to predetermined target rates and channel statistics. Given a fixed transmit power of the WU, both the transmit power and the degree of impropriety of the SU are optimized to minimize the outage probability subject to the outage constraint of the WU. Numerical results are provided to assess the benefits of the proposed IGS-based downlink NOMA system, which are consistent with the analysis.

[The Structure, Expression, and Non-Canonical Functions of Human rDNA: The Role of Non-Coding Regions].

The genes coding for the rRNAs seem evolutionary conserved on the first glance, but astonish one with their variability in the structure and a variety of functions on closer examination. The non-coding parts of rDNA contain regulatory elements, protein binding sites, pseudogenes, repetitive sequences, and microRNA genes. Ribosomal intergenic spacers are not only in charge with the nucleolus morphology and functioning, namely, the rRNA expression and ribosome biogenesis, but also control nuclear chromatin formation thus mediating cell differentiation. The alterations in the expression of these non-coding regions of rDNA in response to environmental stimuli underlie the keen sense of a cell to various types of stressors. Malfunctioning of this process may result in a wide range of pathologies from oncology to neurodegenerative disease and mental illness. Here, we observe to-date materials on the structure and transcription of the ribosomal intergenic spacer in humans and its role in rRNA expression, in-born disease development, and cancer.

Ribosomal Intergenic Spacers Are Filled with Transposon Remnants.

Eukaryotic ribosomal DNA (rDNA) comprises tandem units of highly conserved coding genes separated by rapidly evolving spacer DNA. The spacers of all 12 species examined were filled with short direct repeats (DRs) and multiple long tandem repeats (TRs), completing the rDNA maps that previously contained unannotated and inadequately studied sequences. The external transcribed spacers also were filled with DRs and some contained TRs. We infer that the spacers arose from transposon insertion, followed by their imprecise excision, leaving short DRs characteristic of transposon visitation. The spacers provided a favored location for transposon insertion because they occupy loci containing hundreds to thousands of gene repeats. The spacers' primary cellular function may be to link one ribosomal RNA transcription unit to the next, whereas transposons flourish here because they have colonized the most frequently used part of the genome.

Genetic Clarification of Auricularia heimuer Strains Bred and Cultivated in Korea Using the ITS and IGS1 rDNA Region Sequences.

Auricularia is one of the broadly cultivated edible mushrooms in Korea. Most of the Korean Auricularia strains used for cultivation and breeding are known as A. auricula-judae. Recently, this species has been reported to belong to a species complex. Therefore, this study was carried out to genetically clarify the bred and cultivated Korean A. auricula-judae strains. The internal transcribed spacer (ITS) and IGS1 rDNA region sequences were determined from 10 A. auricula-judae strains by PCR and sequencing. Variation in the nucleotide sequence and sequence length of the two rDNA regions were found among the seven A. auricula-judae strains. A maximum-likelihood (ML) phylogenetic tree based on the ITS sequences clearly placed all the 10 Korean A. auricula-judae strains in the A. heimuer clade of the A. auricula-judae complex. A. heimuer is diverged from A. auricula-judae. An ML phylogenetic tree based on the IGS1 sequences revealed the close relationship between Korean A. heimuer strains to Chinese A. heimuer strains. But each strain could be distinguishable by the IGS1 sequence. Furthermore, progeny strains in the seven Korean strains could be differentiated from their parental strains by the IGS1 sequence based phylogenetic tree. Our results are expected to be used to complement the distinction of domestic Auricularia cultivars.

New insight of human-IgH 3'regulatory regions in immunoglobulins switch.

BACKGROUND: Several studies in animal models have demonstrated the role of the 3' Regulatory Region (3'RR) in the B cell maturation in mammals. In healthy humans, the concentration of each class of circulating immunoglobulins (Igs) has stable but different levels, due to several control mechanisms that also involve a duplicated version of the 3'RR on the chromosome 14 (chr14). The classes' equilibrium can be altered during infections and in other pathological conditions. MATERIAL AND METHODS: We studied the concentrations of IgA, IgM, IgG classes and IgG subclasses in a cohort of 1235 people having immunoglobulin concentrations within normal range to determine the presence of any correlation between the Igs serum concentrations, age and ratio among Ig classes and IgG subclasses in healthy humans. Furthermore, we assessed the concentrations of IgE and the allelic frequency of 3'RR1 hs1.2 enhancer in a group of 115 subjects with high levels of circulating IgE due to acute exacerbation of allergic asthma and in a control group of 118 healthy subjects. RESULTS: In both children and adult subjects, the concentrations of the four IgG subclasses decreased from IgG1 to IgG4. Furthermore, the 3'RR1 enhancer hs1.2 alleles contribute to the control of the IgG subclasses levels, but it does not affect the IgE levels. CONCLUSION: The 3'RR1 controls IgG and IgE through different mechanisms, only in the IgG case involving the hs1.2 alleles. Thus, considering the IgH constant genes loci on the chromosome 14 and the multiple steps of switch that rearrange the whole region, we found that in humans the classes of Igs are modulated by mechanisms involving a complex interaction and transition between 3'RR1 and 3'RR2, also in physiological conditions.

[Assessment of available and currently applied typing methods of zoonotic pathogens using the example of Shiga toxin-producing and enterohemorrhagic Escherichia coli (STEC/EHEC)]. / Bestandsaufnahme der verfügbaren und aktuell eingesetzten Typisierungsmethoden von zoonotischen Erregern am Beispiel von Shiga Toxin-bildenden bzw. enterohämorrhagischen Escherichia coli (STEC/EHEC).

INTRODUCTION: In order to improve patient care and to increase food safety within the framework of One Health, the project "Integrated Genomic Surveillance of Zoonotic Agents (IGS-Zoo)" aims to develop concepts for a genomic surveillance of Shiga toxin(Stx)-producing and enterohemorrhagic Escherichia coli (STEC/EHEC) in Germany. METHODS: An online survey was conducted to assess the currently available and applied STEC/EHEC typing methods in the federal laboratories of veterinary regulation, food control, and public health service. RESULTS: Twenty-six questionnaires from 33 participants were evaluated with regard to STEC/EHEC. The number of STEC/EHEC-suspected samples that the laboratories process per year ranges between 10 and 3500, and out of these they obtain between 3 and 1000 pathogenic isolates. Currently the most frequently used typing method is the determination of Stx- and intimin-coding genes using polymerase chain reaction (PCR). Whole genome sequencing (WGS) is currently used by eight federal state laboratories, and nine are planning to implement it in the future. The most common obstacle for further typing of STEC/EHEC is that isolation from sample material is often unsuccessful despite apparent PCR detection of the stx genes. DISCUSSION: The results of the survey should facilitate the integration of the analysis methods developed in the project and emphasize the target groups' individual needs for corresponding training concepts.

Image-Guided Surgical Device Failures in Functional Endoscopic Sinus Surgery: A MAUDE Analysis.

OBJECTIVE: Image-guided surgery (IGS) devices have become widely used for anatomic localization during functional endoscopic sinus surgery (FESS). However, there are no studies that analyze the post-market complications associated with IGS device use during FESS. The objective of this study was to better characterize post-market complications associated with the use of IGS devices during sinus surgery. METHODS: The US Food and Drug Administration's Manufacturer and User Facility Device Experience database was queried for event reports associated with neurological stereotaxic devices utilized in IGS between the dates of January 1, 2016 and December 31, 2020. Medical device reports that were analyzed for this study pertained strictly to FESS. RESULTS: There were 1873 reports involving IGS devices for FESS included in this study. Fifty-five reports involved adverse events to patients (2.9%) and 1818 (97.1%) involved device malfunctions. Of the adverse events to patients, the most common included cerebrospinal fluid leakage (45.6%), tissue damage (12.7%), and nervous system injury (3.6%). The most commonly reported device malfunction was imprecision (21.1%). CONCLUSION: IGS devices are widely utilized in FESS. Of the medical device reports between 2016 and 2020, less than 3% resulted in adverse events. Further studies of the infrequent post-market complications of IGS devices used in FESS can help guide surgeons on the risks of their clinical use. LEVEL OF EVIDENCE: 4-Retrospective database survey without controls Laryngoscope, 133:1310-1314, 2023.

Molecular Typing on Human Blood Reveals the Borrelia afzelii Infection in Korea.

Lyme disease is a tick-borne infection in Korea. Here, clinical samples were collected from a 72-year old patient, with sudden onset of fever on April, 2018. The patient was passed away after 3rd day of doxycycline administration. The molecular diagnostic tests, nested polymerase chain reaction targeting 5S-23S rRNA intergenic spacer region (IGS) and multilocus sequence typing (MLST), showed positive for Borrelia afzelii from blood. Further, mutations in both 5S - 23S IGS and pepX allele of MLST were determined. Herein, we report the expected first death case by B. afzelii infection in Korea.

Molecular Characterization of Aspergillus flavus Strains Isolated from Animal Feeds.

Aflatoxin (AF)-producing fungi such as Aspergillus flavus commonly contaminate animal feeds, causing high economic losses. A. flavus is the most prevalent and produces AFB1, a potent mutagen, and carcinogen threatening human and animal health. Aspergillaceae is a large group of closely related fungi sharing number of morphological and genetic similarities that complicate the diagnosis of highly pathogenic strains. We used here morphological and molecular assays to characterize fungal isolates from animal feeds in Southwestern Algeria. These tools helped to identify 20 out of 30 Aspergillus strains, and 15 of them belonged to the Aspergillus section Flavi. Further analyses detected four out of 15 as belonging to Aspergillus flavus-parasiticus group. PCR targeting the AF genes' aflR-aflS(J) intergenic region amplified a single 674 bp amplicon in all four isolates. The amplicons were digested with a BglII endonuclease, and three specific fragments were observed for A. flavus but A. parasitucus lacked two typical fragments. Sequencing data of four amplicons confirmed the presence of the two BglII restriction sites yielding the three fragments, confirming that all four strains were A. flavus. In addition, this analysis illustrated the genetic variability within the A. flavus strains.

Structure and Methylation of 35S rDNA in Allopolyploids Anemone multifida (2n = 4x = 32, BBDD) and Anemone baldensis (2n = 6x = 48, AABBDD) and Their Parental Species Show Evidence of Nucleolar Dominance.

Transcriptional silencing of 35S rDNA loci inherited from one parental species is occurring relatively frequently in allopolyploids. However, molecular mechanisms by which it is selected for transcriptional silencing remain unclear. We applied NGS, silver staining and bisulfite sequencing to study the structure, expression and methylation landscape of 35S rDNA in two allopolyploids of common origin, allotetraploid Anemone multifida (2n = 4x = 32, genome composition BBDD) and allohexaploid A. baldensis (2n = 6x = 48, AABBDD), and their genome donors, A. sylvestris (2n = 16, AA), A. cylindrica (2n = 16, BB) and A. parviflora (2n = 16, DD). The size of the recovered 35S rDNA units varied from 10,489 bp in A. cylindrica to 12,084 bp in A. sylvestris. Anemone showed an organization typical of most ribosomal 35S rDNA composed of NTS, ETS, rRNA genes, TTS and TIS with structural features of plant IGS sequences and all functional elements needed for rRNA gene activity. The NTS was more variable than the ETS and consisted of SRs which are highly variable among Anemone. Five to six CpG-rich islands were found within the ETS. CpG island located adjacent to the transcription initiation site (TIS) was highly variable regarding the sequence size and methylation level and exhibited in most of the species lower levels of methylation than CpG islands located adjacent to the 18S rRNA gene. Our results uncover hypomethylation of A. sylvestris- and A. parviflora-derived 35S rDNA units in allopolyploids A. multifida and A. baldensis. Hypomethylation of A. parviflora-derived 35S rDNA was more prominent in A. baldensis than in A. multifida. We showed that A. baldensis underwent coupled A. sylvestris-derived 35S rDNA array expansion and A. parviflora-derived 35S rDNA copy number decrease that was accompanied by lower methylation level of A. sylvestris-derived 35S rDNA units in comparison to A. parviflora-derived 35S rDNA units. These observations suggest that in A. baldensis nucleolar dominance is directed toward A. sylvestris-derived chromosomes. This work broadens our current knowledge of the 35S rDNA organization in Anemone and provides evidence of the progenitor-specific 35S rDNA methylation in nucleolar dominance.

Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW.

Fluorescence image-guided surgery (IGS) using antibody conjugates of the fluorophore IRDye800CW have revolutionized the surgical debulking of tumors. Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, conjugated to IRDye800CW (Cet-IRDye800) is the first molecular targeted antibody probe to be used for IGS in head and neck cancer patients. In addition to surgical debulking, Cetuximab-targeted photodynamic therapy (photoimmunotherapy; PIT) is emerging in the clinic as a powerful modality for head and neck tumor photodestruction. A plethora of other photoactivable agents are also in clinical trials for photodynamic-based therapies of head and neck cancer. Considering the vascular and stromal modulating effects of sub-therapeutic photodynamic therapy, namely photodynamic priming (PDP), this study explores the potential synergy between PDP and IGS for a novel photodynamic image-guided surgery (P-IGS) strategy. To the best of our knowledge, this is the first demonstration that PDP of the tumor microenvironment can augment the tumor delivery of full-length antibodies, namely Cet-IRDye800. In this study, we demonstrate a proof-of-concept that PDP primes orthotopic FaDu human head and neck tumors in mice for P-IGS by increasing the delivery of Cet-IRDye800 by up to 138.6%, by expediting its interstitial accumulation by 10.5-fold, and by increasing its fractional tumor coverage by 49.5% at 1 h following Cet-IRDye800 administration. Importantly, PDP improves the diagnostic accuracy of tumor detection by up to 264.2% with respect to vicinal salivary glands at 1 h. As such, PDP provides a time-to-surgery benefit by reducing the time to plateau 10-fold from 25.7 h to 2.5 h. We therefore propose that a pre-operative PDP regimen can expedite and augment the accuracy of IGS-mediated surgical debulking of head and neck tumors and reduce the time-to-IGS. Furthermore, this P-IGS regimen, can also enable a forward-looking post-operative protocol for the photodestruction of unresectable microscopic disease in the surgical bed. Beyond this scope, the role of PDP in the homogenous delivery of diagnostic, theranostic and therapeutic antibodies in solid tumors is of considerable significance to the wider community.

Study and Physical Mapping of the Species-Specific Tandem Repeat CS-237 Linked with 45S Ribosomal DNA Intergenic Spacer in Cannabis sativa L.

Hemp (Cannabis sativa L.) is a valuable crop and model plant for studying sex chromosomes. The scientific interest in the plant has led to its whole genome sequencing and the determination of its cytogenetic characteristics. A range of cytogenetic markers (subtelomeric repeat CS-1, 5S rDNA, and 45S rDNA) has been mapped onto hemp's chromosomes by fluorescent in situ hybridization (FISH). In this study, another cytogenetic marker (the tandem repeat CS-237, with a 237 bp monomer) was found, studied, and localized on chromosomes by FISH. The signal distribution and karyotyping revealed that the CS-237 probe was localized in chromosome 6 with one hybridization site and in chromosome 8 with two hybridization sites, one of which colocalizes with the 45S rDNA probe (with which a nucleolus organizer region, NOR, was detected). A BLAST analysis of the genomic data and PCR experiments showed that the modified CS-237 monomers (delCS-237, 208 bp in size) were present in the intergenic spacers (IGSs) of hemp 45S rDNA monomers. Such a feature was firstly observed in Cannabaceae species. However, IGS-linked DNA repeats were found in several plant species of other families (Fabaceae, Solanaceae, and Asteraceae). This phenomenon is discussed in this article. The example of CS-237 may be useful for further studying the phenomenon as well as for the physical mapping of hemp chromosomes.

Biochemical, dielectric and surface characteristics of freeze-dried bovine colostrum whey powder.

Colostrum samples of recently registered cow breed "Himachali Pahari" were assorted from high altitude zone (901-2200 m). Prepared bovine colostrum whey powder (BCWP) was analysed for chemical composition, amino acids, minerals, surface morphology (SEM-EDS), FTIR and dielectric properties. Results showed that freeze-dried BCWP contained a considerable amount of nutritional parameters viz IgG (18.55 g/100 g), protein (71.72 g/100 g) and total amino acids (69.64 g/100 g). Additionally, the concentration of essential minerals was found to be adequate, and there was no presence of heavy metals. The BCWP exhibits good dielectric properties (resistance ∼57 M-Ω). SEM-EDS showed the broken up-wards layer structure with the uniform distribution of minerals on the surface. The FTIR spectra confirmed the presence of a higher proportion of ß-sheets and ß-turn structures in BCWP. Thus, on account of good functional and nutritive properties, BCWP could be foreseen as the future of functional food.