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Judging whether an editor is good at the job is essential; however, this task may be difficult or even impossible. Several factors are involved, many of which are beyond the control of an editor. We examined some of such situations, which are as follows: (1) Reviewer's abuse of privileged information, in which a reviewer or an associate, who is likely to be a competitor, directs members of their laboratory to rapidly replicate the data and submit the resulting paper in the same or another journal while delaying publication of the submitted paper; (2) defective micromanagement by a stakeholder or owner, such as failure to order paper for the publication of a journal; (3) penny-wise dollar-foolish mismanagement by the owner, such as limiting the figures allowed to an absurdly low number in a dermatology journal (we have a visual specialty); (4) factional abuse, such as when members of a society use a gimmick to exercise outsized influence to effect a change in journal's content, and (5) " sto tavo (who is in charge)?," in which changes in the governance of an ownership society or publisher affect quality of the journal.

We describe a novel assay and artificial intelligence-driven histopathologic approach identifying dermatophytes in human skin tissue sections (ie, B-DNA dermatophyte assay) and demonstrate, for the first time, the presence of dermatophytes in tissue using immunohistochemistry to detect canonical right-handed double-stranded (ds) B-DNA. Immunohistochemistry was performed using anti-ds-B-DNA monoclonal antibodies with formalin-fixed paraffin-embedded tissues to determine the presence of dermatophytes. The B-DNA assay resulted in a more accurate identification of dermatophytes, nuclear morphology, dimensions, and gene expression of dermatophytes (ie, optical density values) than periodic acid-Schiff (PAS), Grocott methenamine silver (GMS), or hematoxylin and eosin (H&E) stains. The novel assay guided by artificial intelligence allowed for efficient identification of different types of dermatophytes (eg, hyphae, microconidia, macroconidia, and arthroconidia). Using the B-DNA dermatophyte assay as a clinical tool for diagnosing dermatophytes is an alternative to PAS, GMS, and H&E as a fast and inexpensive way to accurately detect dermatophytosis and reduce the number of false negatives. Our assay resulted in superior identification, sensitivity, life cycle stages, and morphology compared to H&E, PAS, and GMS stains. This method detects a specific structural marker (ie, ds-B-DNA), which can assist with diagnosis of dermatophytes. It represents a significant advantage over methods currently in use., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Commonly used dermatologic eponyms and characteristic skin signs are enormously helpful in guiding a diagnosis, even though they may not be pathonemonic. They include, on the nails, Aldrich-Mees' lines (syn.: Mees' lines), Beau's lines, Muehrcke's lines, Terry's nails, and half and half nails, often associated, respectively, with arsenic poisoning, acute stress or systemic illness, severe hypertension, liver disease and uremia, and, around the nails, Braverman's sign, associated with collagen-vascular disease. Elsewhere, one may see the Asboe-Hansen and Nikolsky's signs, indicative of the pemphigus group of diseases, Auspitz's sign, a classic finding in psoriasis, Borsieri's and Pasita's signs, seen in early scarlet fever, the butterfly rash, indicative of systemic lupus erythematosus, and the buffalo hump, seen in Cushing's disease and also in the more common corticosteroid toxicity. Gottron's papules and the heliotrope rash are signs of dermatomyositis. Janeway's lesions and Osler's nodes are seen in bacterial endocarditis. A Dennie-Morgan fold under the eye is seen in association with atopic disease. Koplik's spots are an early sign of rubeola. Fitzpatrick's sign is indicative of a benign lesion (dermatofibroma), whereas Hutchinson's sign is indicative of a malignant one (subungual melanoma). Petechiae are seen in many diseases, including fat embolization, particularly from a large bone fracture following trauma. Palpable purpura is indicative of leukocytoclastic vasculitis, and is an early, critical sign in Rickettsial diseases, including Rocky Mountain Spotted Fever, which must be diagnosed and treated early. Hyperpigmentation of areolae and scars is seen in Addison's disease. Acanthosis nigricans may indicate internal cancer, especially stomach cancer, whereas Bazex's syndrome occurs in synchrony with primary, usually squamous cancer, in the upper aerodigestive tract or metastatic cancer in cervical lymph nodes. Perioral pigmented macules or one or more cutaneous sebaceous neoplasms may be a sign of the Peutz-Jeghers or Muir-Torre syndrome, respectively, both associated also with intestinal polyps that have a malignant potential. Telangiectasiae in the perioral region may be associated with similar lesions internally in Osler-Weber-Rendu disease. Kerr's sign is indicative of spinal cord injury and Darier's sign of mastocytosis. Post proctoscopic periobital purpura (PPPP) is a phenomenon observed in some patients with systemic amyloidosis. Koebner's isomorphic response refers to the tendency of an established dermatosis, such as psoriasis, to arise in (a) site(s) of trauma, whereas Wolf's isotrophic response refers to a new dermatosis, such as tinea, not yet seen in the patient, arising in (a) site(s) of a former but different dermatosis, such as zoster., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Although the term, "trichothiodystrophy" (TTD) refers to the hair anomalies in this group of patients, this is a heterogeneous, multisystem disease in which any or every organ in the body may be affected. Neuroectodermal derived tissues are particularly likely to be involved. This term was introduced by Price et alin 1980 to designate patients with sulfur-deficient brittle hair, which they recognized as a marker for this complex disease and designated it as a "neuroectodermal symptom complex". Patients with TTD have brittle hair and nails (associated with reduced content ofcysteine-rich matrix proteins), ichthyotic skin and physical and mental growth retardation. Ichthyosis is usually apparent at birth but much less so after the first few weeks of life. Other frequently associated features include ocular cataracts, infections and maternal complications related to pregnancy. Atrophy of subcutaneous fat may also be present. TTD occurs in a pattern of inheritance consistent with an autosomal recessive condition. The disease is extremely heterogeneous in severity and extent, with some patients showing no neurological deficiency. Others show severe, multisystem disease. Many patients die at a young age, most commonly due to infectious disease. TTD is part of a more broadly defined group of diseases identified as IBIDS (ichthyosis, brittle hair, impaired intelligence, decreased fertility and short stature). Photosensitive cases are also identified as PIBIDS (photosensitivity with IBIDS). Cases without manifest ichthyosis are also identified as PBIDS. These syndromes defy rigorous definition because of clinical variation between patients. The original two cases were described by Tay in oriental siblings, whose parents were first cousins; thus the disease is also known as Tay syndrome. The hairs in patients with TTD have a distinctive, diagnostically useful appearance on polarized light microscopy consisting of alternating light and dark bands known as the "tiger tail" anomaly. Diagnosis may be confirmed by sulfur content analysis ofhair shafts, which shows decreased sulfur and cysteine content. Approximately half of patients with TTD have photosensitivity, which correlates with a nudeotide excision repair (NER) defect. These patients are designated as having trichothiodystrophy-photosensitive (TTDP). Non-photosensitivepatients are designated as having trichothiodystrophy-nonphotosensitive (TTDN). Skin cancer is very rare in sun-sensitive TTD.

Quantification of two types of nucleic acids [double-stranded (ds-) and single-stranded (ss-) DNA] was performed to understand the distribution of DNA within the epidermal strata and to examine the effects of DNA structure on gene expression, viz., apoptosis and terminal differentiation. In addition, we examined the precise starting point of cell death within the epidermis (suprabasal layer); examined how DNA structure affects gene expression of melanocytes; and characterized the "transitional cells" located between the stratum granulosum and stratum corneum, viz., epidermal phase transition zone (EPTZ). Ultrasensitive anti-DNA antibody probes (ds-DNA, ss-DNA), the Feulgen reaction, histological stains (morphological characterization) and the terminal deoxyribonucleotidyl transferase (TUNEL) assay (apoptosis) were used to characterize cell death in normal human epidermis. This study characterized, for the first time, the deterioration of right-handed ds-B-DNA and the increase in denatured ss-DNA during epidermal maturation. For the first time, this approach also allowed for the quantitative and qualitative characterization of DNA content and structure in all epidermal strata, using anti-ds-B-DNA and anti-ss-DNA antibodies. In order to improve the retention and quality of DNA, a novel histotechnological processing procedure was used. The results indicate that the largest decline in DNA occurred within the stratum granulosum, followed by the EPTZ, and the stratum spinosum. Not all epidermal nuclei lost DNA, indicating two differentiating keratinocyte pathways, viz., apoptotic and non-apoptotic. Both pathways united in the stratum granulosum. These results suggest that keratinocyte terminal differentiation and apoptosis are distinct cellular events, cell death begins earlier than expected, and molecular epidermal events take place in a gradual and orderly manner within keratinocytes. During maturation, ds-B-DNA decreases as ss-DNA increases. Therefore, during differentiation of keratinocytes, both DNA content and DNA structure are altered.

Novel multistranded and alternative DNA, RNA and plasmid microarrays (transitional structural nucleic acid microarrays) have been developed that allows for the immobilization of intact, nondenatured, double-stranded DNA, double-stranded RNA, and alternative and multistranded nucleic acids. It also allows for the study of transitional changes that occur in the structure of DNA and RNA. Alternative types of DNA, RNA and multistranded nucleic acids are immobilized by a variety of different surface chemistries (i.e., noncovalent or covalent) onto a novel substrate surface. This technology represents the next generation of microarrays, which will aid in the characterization of nucleic acid structure and function, and accelerate the discovery of drugs that bind to nucleic acids. In addition, we demonstrate four novel techniques that are the first practical applications of the microarray, that is, transitional structural chemogenomics, transitional structural chemoproteomics, transitional structural pharmacogenomics and transitional structural pharmacoproteomics. These novel nucleic acid microarrays, together with pharmacogenomics, can be used to improve the study of DNA and RNA structure, gene expression, drug development and treatment of various diseases.

It is our working hypothesis that the high rate of the liver and gastric cancers in North and Northeast Thailand is associated with increased daily dietary intake of nitrate, nitrite, and nitrosodimethylamine (NDMA). Samples of fresh and preserved Thai foods were systematically collected and analyzed from 1988 to 1996 and from 1998 to 2005. Consumption frequencies of various food items were determined on the basis of a dietary questionnaire given to 467 adults (212 males and 255 females) from 1998 to 2005. Food consumption data for the preceding and current year were collected and intakes (day, week, and month) of nitrate, nitrite, and NDMA were calculated. The trends in liver and stomach cancer age-standardized incidence rates (ASR) in four regions of Thailand were compared with the dietary intake of nitrate, nitrite, and NDMA in those same geographic regions. Mean daily intakes of nitrate of 155.7 mg/kg, of nitrite of 7.1 mg/kg, and of NDMA of 1.08 microg/kg per day were found. Significant differences in dietary nitrate, nitrite, and NDMA intakes were seen between various Thai regions (P < 0.0001), and these corresponded to the variations in liver and stomach cancer ASR values between the regions. Dietary factors are likely to play key roles in different stages of liver and stomach carcinogenesis in Thailand.

Histotechnological processing of DNA can cause damage to and loss of DNA and can change its structure. DNA probes have severe tissue-staining limitations. New DNA probes and improved histotechnology are needed to enhance the characterization of fixed tissue-bound DNA. Our team developed a novel DNA staining technique and histotechnological processing procedure that improves tissue-bound DNA retention and the qualification and quantification of intact double-stranded (ds)-B-DNA. We used the ultrasensitive PicoGreen ds-DNA probe for the histochemical characterization of ds-DNA. Fifteen fixatives were examined to determine which were best for preventing DNA denaturation and retaining original DNA content and structures. Our use of a microwave-vacuum oven reduced heating temperatures, shortened heating and processing times, and enhanced fixation. We achieved better qualitative and quantitative results by using superior tissue-acquisition techniques (e.g., reduced prefixation times) and improved histotechnology. We also compared our novel approach with archival tissues, delayed fixation, less sophisticated and conventional histological processing techniques, and by experimenting with preservation of tissue-bound ds-Z-DNA. Results demonstrate that our histotechnological procedure and nucleic acid staining method significantly improve the retention of intact, undamaged ds-DNA which, in turn, allows the investigator to more precisely quantify the content and structures of unaltered and undamaged tissue-bound ds-B-DNA.

Cell biology has added immensely to the understanding of basic biologic concepts. However, scientists need to use cell biology more in the proteomic-genomic revolution. The authors have developed two novel techniques: transitional structural chemogenomics (TSCg) and transitional structural chemoproteomics (TSCp). TSCg is used to regulate gene expression by using ultrasensitive small-molecule drugs that target nucleic acids. By using chemicals to target transitional changes in the helical conformations of single-stranded (ss) and double-stranded (ds) DNA (e.g., B- to Z-DNA) and RNA (e.g., A- to Z-RNA), gene expression can be regulated (i.e., turning genes 'on/off' and variably controlling them). Alternative types of ds- and ssDNA and RNA (e.g., cruciform DNA) and other multistranded nucleic acids (e.g., triplex-DNA) are also targeted by this method. The authors' second technique, TSCp, targets a protein before, during or after post-translational modifications, which alters the protein's structure and function. These novel methods represent the next step in the evolution of chemical genomics and chemical proteomics. In addition, a novel multi-stranded (alternative) DNA, RNA and plasmid microarray has been developed that allows for the immobilization of intact, non-denatured dsDNA, alternative (i.e., exotic) and other multiple-stranded nucleic acids. This represents the next generation of nucleic acid microarrays, which will aid in the characterization of nucleic acids, studying the ageing process and improving the drug discovery process. The authors discuss how cell biology can be used to enhance genomics and proteomics. Cell biology will play a greater role during the postgenomic age and will help to enhance the omics/omes and drug discovery. It is the authors' hope that these novel approaches can be used together with cellular biologic techniques to make major contributions towards understanding and manipulating different genomes.

Nucleic acids and proteins are dynamic molecules that undergo structural changes which control gene expression. The authors have developed two novel techniques, viz., transitional structural chemogenomics and transitional structural chemoproteomics. Transitional structural chemogenomics is used to regulate gene expression, employing ultrasensitive small-molecule drugs targeted toward nucleic acids. Gene expression can be regulated by using chemicals to target transitional changes in the helical conformations of single-stranded (ss-) and double-stranded (ds-) DNA (e.g., B- to Z-DNA), and RNA (e.g., A- to Z-RNA). This method also targets alternative types of ds- and ss-DNA and RNA (e.g., cruciform DNA), and other multi-stranded nucleic acids (e.g., triplex-DNA). Our second technique, transitional structural chemoproteomics, targets a protein before, during or after post-translational modifications which alters its structure and function. Both a proteins' structured and unstructured regions are targeted. These two novel methods represent the next step in the evolution of chemical genomics and chemical proteomics. They allow for two approaches to regulate gene expression, viz., turning genes "on", "off" or variable control (e.g., dimmer switch). This article also discusses the confusion that exists between the term chemical genomics and other related subdisciplines, such as chemical proteomics. Additionally, we have developed a novel multi-stranded DNA, RNA and plasmid microarray which immobilizes intact nondenatured ds-DNA, alternative, and other multiple-stranded nucleic acids onto a substrate surface. This technique represents the next generation of nucleic acid microarrays, which will enhance the characterization of nucleic acids and the drug discovery process. These three novel techniques allow for a multifaceted approach that will greatly enhance the success of molecular biology, the "omics" and drug discovery. They represent the next era of gene expression tools.

The scientific techniques used in molecular biological research and drug discovery have changed dramatically over the past 10 years due to the influence of genomics, proteomics and bioinformatics. Furthermore, genomics and functional genomics are now merging into a new scientific approach called chemogenomics. Advancements in the study of molecular cell biology are dependent upon "omics" researchers realizing the importance of and using the experimental tools currently available to cell biologists. For example, novel microscopic techniques utilizing advanced computer imaging allow for the examination of live specimens in a fourth dimension, viz., time. Yet, molecular biologists have not taken full advantage of these and other traditional and novel cell biology techniques for the further advancement of genomic and proteomic-oriented research. The application of traditional and novel cellular biological techniques will enhance the science of genomics. The authors hypothesize that a stronger interdisciplinary approach must be taken between cell biology (and its closely related fields) and genomics, proteomics and bio-chemoinformatics. Since there is a lot of confusion regarding many of the "omics" definitions, this article also clarifies some of the basic terminology used in genomics, and related fields. It also reviews the current status and future potential of chemogenomics and its relationship to cell biology. The authors also discuss and expand upon the differences between chemogenomics and the relatively new term--chemoproteomics. We conclude that the advances in cell biology methods and approaches and their adoption by "omics" researchers will allow scientists to maximize our knowledge about life.

Forty-nine years ago Watson and Crick proposed a double-stranded (ds-) model for DNA. This double helix has become an icon of molecular biology. Twenty-six years later, Rich accidently discovered Z-DNA, an exotic left-handed nucleic acid. For many years thereafter, this left-handed DNA was thought to be an artifact. DNA is no longer looked upon as a static molecule but rather an extremely dynamic structure in which different conformations are in equilibrium with each other. Many researchers have spent the last two decades characterizing this novel left-handed DNA structure. Now many investigators are beginning to accept the possibility that this novel ds-DNA conformation may play a significant in vivo role within eukaryotic and prokaryotic cells. However, more research needs to be performed before it is absolutely accepted by all in the scientific community.

Using a novel immunocytochemical staining method, we aimed to characterize the phase transition zone (PTZ) (approximatly 100 microm) in adult ocular lenses and the process of terminal differentiation (denucleation) within normal fiber cells. The binding to DNA of zeta-(zeta) crystallin (Z-DNA-binding protein) and anti-double-stranded (ds-)-B-DNA antibody probes was found to decline gradually throughout denucleating fibers, with a precipitous decrease occurring at about 100 microm (PTZ). Nuclei of superficial fiber cells (in front of the PTZ) showed the highest DNA probe-binding values, followed by middle fibers (MF) and deep fibers (DF). With the use of zeta-crystallin, anti-ds-B-DNA antibody, and anti-single stranded (ss-) DNA antibody probes, it was possible to reveal a loss of reactivity of fiber cell ds-DNA. Ss-DNA antibody binding was seen initially in the MF and reached its highest intensity level in the DF. The pattern of zeta-crystallin probe-DNA reactivity correlates with the loss of anti-B-DNA antibody staining and decreased eosin-protein staining. These data suggest that a reorganization of DNA and intracellular protein supramolecular order in normal adult lenses occurs at a depth of about 100 microm (PTZ).

Apoptosis is the ordered chain of events that lead to cell destruction. Terminal differentiation (denucleation) is the process in which cells lose their nuclei but remain functional. Our group examined cell death in three tissues using two different fixatives and a postfixation procedure, involving young (5 months) and old (2 years) guinea pigs. The data reveal that B-DNA and Z-DNA content decreases, whereas single-stranded (ss-) DNA increases, in older tissues undergoing apoptosis (skin and cornea) and terminal differentiation (ocular lens). We speculate that some of the factors that contribute to the aging process might also be responsible for the enhanced amount of damaged DNA in older tissues undergoing cell death. (J Histochem 49:929-930, 2001)

Nucleic acids control the expression of genes, and different conformations of DNA structure may regulate cell death. Left-handed Z-DNA, which is speculated to function as a transcriptional enhancer, may be directly influenced by the destructive effects of terminal differentiation. The nicking-denaturation of double-stranded Z-DNA could possibly initiate and enhance terminal differentiation within specific tissues.

Bovine zeta-crystallin has the ability to bind with different DNAs. Initially, this protein was named regulatory factor 36 (Kang et al., 1985), but it has been shown to be an ocular lens zeta-crystallin (Jörnvall et al., 1993), which is considered an enzyme-crystallin (Rodakanaki et al., 1989). The enzyme-linked immunosorbent assay (ELISA) was used to quantitate the binding of bovine zeta-crystallin to purified high molecular weight double-stranded (ds-) and single-stranded (ss-) DNA (bovine and synthetic DNA). ELISA quantitation was achieved by the addition of anti-zeta-crystallin antibodies to the DNA-zeta-crystallin complex, using a novel immunochemical avidin-biotin method. Zeta-crystallin shows much greater binding intensity for ss-DNA and for ds-Z-DNA than for ds-B-DNA. It also reacts slightly more with ds-Z-DNA than ss-DNA. Therefore, we speculate that zeta-crystallin may act as a transcriptional enhancer (outer lens cortex), possibly binding to Z-DNA regulatory elements within lens crystallin genes. It may also act to protect DNA from endogenous DNase activity and as a DNA unwinding (destabilizing) protein also involved with transcription, occurring in normal adult bovine lens nucleated secondary fiber cells.

We examined histochemically and immunohistochemically the distribution of B- and Z-DNA in the epithelium and terminally differentiating dog lens fiber cells. On the basis of anti-DNA antibody reactivity, qualitative and quantitative data on B- and Z-DNA in cells were determined. Anti-B-DNA immunoreactivity gradually declined throughout nucleated fibers, with a precipitous decrease at approximately 90 microns. Anti-Z-DNA antibody binding decreased with a sudden loss of immunoreactivity at approximately 90 microns. The pattern of anti-B- and Z-DNA staining correlates with the loss of alpha-crystallin immunoreactivity, the major lens crystallin, and decreased eosin staining of proteins. Germinative zone cell nuclei showed the highest DNA probe binding values, followed by the superficial fibers, central zone, middle fibers, and deep fibers. The presence of single-stranded (ss)DNA in deeper fibers was detected by anti-ss-DNA antibodies. This is indicative of DNA degradation. These observations suggest that a dramatic reorganization of lens fiber cells' supramolecular order occurs at approximately 90 microns, the phase transition zone.

The purpose of this study was to reveal the presence of Z-helical conformation in normal crystalline lens DNA. Z-DNA antigen was prepared against poly(dG-dC).poly(dG-dC), which had been converted to the Z-helix conformation in high salt and then stabilized by bromination. Circular dichroism (CD) spectra confirmed the presence of left-handed Z-helix DNA. Antibodies to Z-DNA were raised in three rabbits immunized with brominated (Br-) poly(dG-dC).poly(dG-dC). These antibodies do not cross-react with polynucleotides in the B-helical form, but are specific to the left-handed Z-DNA conformation. DNA was isolated from three different regions of the calf lens. Anti-Z-DNA antisera, affinity purified IgG polyclonal anti-Z-DNA antibodies and monoclonal anti-Z-DNA antibodies were used as immunoprobes to detect the presence of S-DNA sequences. DNA from the cortex region of the lens reacted strongly with the anti-Z-DNA antibodies, but no binding could be observed in the DNA from the nucleus region. Digestion of lens DNA with DNase 1 dramatically decreased Z-DNA antibody binding, while RNase A and T1 treatment had no effect on Z-DNA immunoreactivity. This study has demonstrated that: (a) Z-DNA antibodies developed for our study can bind in high salt solutions (4M NaCl) to purified lens DNA sequences isolated from a variety of different calf lens cell types. By this criterion, lens DNA contains sequence determinants which may assume or are in the Z-helix conformation.

In order to establish the presence of Z-DNA sequences in the normal crystalline lens and to define their structure-function relationship, fixed and unfixed calf lens tissue sections were examined immunohistochemically. Polyclonal and monoclonal anti-Z-DNA antibodies were developed as immunoprobes, using brominated (Br-) poly(dG-dC).poly(dG-dC) as an antigen. The structure of the Z-helix antigen was confirmed by circular dichroism (CD) and U.V. spectroscopy. Whole rabbit and goat anti-Z-DNA sera; rabbit and goat IgG polyclonal anti-Z-DNA antibodies; and anti-Z-DNA monoclonal IgG antibodies were utilized as Z-DNA immunoprobes to localize the Z-DNA in calf lens tissue sections. Immunohistochemical examination using the peroxidase-antiperoxidase (PAP) method indicated that the cortex region of the lens reacted strongly with the anti-Z-DNA antibodies, while no immunoreaction could be observed in the nucleus region. Similar immunoreactive patterns were obtained whether whole sera, affinity purified IgG polyclonal antibodies or monoclonal antibodies were utilized. Immunobinding of anti-Z-DNA antibodies was low, effectively background type binding, in unfixed lens tissue sections. Various fixatives were tested to explore the potential antibody-Z-DNA interaction in calf lens tissue. Nuclear fixatives enhanced Z-DNA antibody immunoreactivity, while formalin, microanatomic and cytoplasmic fixatives produced lesser results. Digestion of the lens tissue with DNase I eliminated Z-DNA immunoreactivity, while RNase A and RNase T1 treatment had no effect. Actinomycin D also prevented Z-DNA immunoreactivity.