Suppression of Nonlinear Optical Rogue Wave Formation Using Polarization-Structured Beams.

A nonlinear self-focusing material can amplify random small-amplitude phase modulations present in an optical beam, leading to the formation of amplitude singularities commonly referred to as optical caustics. By imposing polarization structuring on the beam, we demonstrate the suppression of amplitude singularities caused by nonlinear self-phase modulation. Our results are the first to indicate that polarization-structured beams can suppress nonlinear caustic formation in a saturable self-focusing medium and add to the growing understanding of catastrophic self-focusing effects in beams containing polarization structure.

Expression of mBD4, mBD3 and CRAMP during type II collagen-induced arthritis/CIA and their association with inflammation and bone-remodeling markers.

The aim of this study was to analyze the expression of mBD4, mBD3 and CRAMP in joint of mice with type II collagen-induced arthritis/CIA and to explore its possible association with IL-10, IL-4, IFN-γ, IL-17, MMP3, RANK/RANKL/OPG and histological parameters. METHODS: CIA was induced in 44 DBA/1 J mice. The joints from mice were classified into the onset, peak and remission phase of CIA. Histological sections were stained with hematoxylin-eosin and safranin O. The expression of CRAMP, mBD-3, mBD-4, and MMP-3 was evaluated using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The expression of IL-10, IL-4, IFN-γ, IL-17, RANK/RANKL/OPG was analyzed by RT-PCR. RESULTS: We observed that inflammation and immunostained cells for CRAMP increased in the peak and remission phases compared to the control group. In addition, increments in relative expressions of CRAMP were detected for the remission phase and in IL-4 and IL-17 in the peak phase compared to the control and onset phase. In addition, an increase in IL-10 in a peak phase compared to the control, as well as the relative expression of IFN-γ in remission phase was higher than in the onset phase. This was accompanied by an increase in cartilage damage in the peak phase compared to the control. Cells immunostained to MMP3 increased in the peak phase compared to the onset and control group, and relative expression of MMP3 was detected in the peak phase compared to the onset, remission, and control group. We observed that the relative expression of RANK and RANKL in the peak phase was higher than in control and onset phase. Finally, the relative expression of OPG in the peak phase compared to the onset, remission, and control group was detected. Regarding CRAMP behavior in the different phases studied, it was positively correlated with IL-4 and RANK, and showed a negative correlation with IFN-γ, IL-17, IL-10, RANKL, OPG and RANKL/OPG ratio in the control group. Also was positively correlated with IFN-γ, IL-17, IL-4, IL-10, as well as with RANK, RANKL, and OPG in the onset and peak phases of the CIA. In the peak phase, CRAMP showed a positive association with MMP3, and we observed a direct correlation between CRAMP and IFN-γ and RANKL/OPG ratio in remission phase. mBD3 correlates positively with IFN-γ, IL-17, IL-10, RANKL, OPG and RANKL/OPG ratio, and showed a negative correlation with CRAMP, MMP3, and RANK in the control group. Also, it was directly associated with IFN-γ, IL-17, IL-4, IL-10 and RANKL in the onset phase while it was inversely associated with CRAMP, MMP-3, RANK, RANKL, and OPG in the peak phase. Finally, mBD3 was inversely correlated with MMP3 in the remission phase and was directly associated with CRAMP, IFN-γ and RANKL/OPG ratio in this phase. mBD4 was directly associated with CRAMP, IFN-γ, IL-17, IL-4, IL-10, RANKL / OPG in the onset phase, and with CRAMP, IFN-γ, IL-17, IL-4, IL-10, MMP3, RANK, RANKL and OPG in the peak phase. Finally, mBD4 was positively associated with mBD3, IFN-γ, IL-17, IL-10, RANK, RANKL OPG and RANKL/OPG in the CIA remission phase. CONCLUSIONS: Our results demonstrate that CRAMP plays an important role in CIA progress and suggest that its abundance is associated with local pro- and anti-inflammatory status. This makes us propose CRAMP as a possible contributor of bone reconstruction in the last stage of CIA.

Tropical milk production systems and milk quality: a review.

We reviewed information on dairy cattle production systems in the tropics, the factors involved, and their influence on milk composition. Genetic factors had greater influence on milk production; specialized breeds produced more milk, and there was an inverse relation between the content of fat, protein, total solids, and the amount of milk produced. Season was related to the availability of forage, and the type of grazing system. Greater pasture area increased individual production, while a greater supply of feed concentrate did not increase milk production. The number of calvings positively affected milk production through the fifth calving, with subsequent declines in production. Milk production increased to a maximum and then declined as lactation progressed. Specialized systems had higher production and better hygienic milk quality; milking and container equipment are critical for maintaining milk sanitary quality. Factor interaction is highly complex, preventing the generation of specific recommendations and general principles applicable to the specific conditions for each system.

Assessing long-term return to play after hip arthroscopy in football players evaluating risk factors for good prognosis.

PURPOSE: Groin pain is the third most common disease in football players and has often been associated with hip pathology such as femoroacetabular impingement and labral lesions. Hip arthroscopy offers possibilities of function restoration via minimally invasive procedures. The aim of this study is to evaluate professional football player's injuries and their return to play after hip arthroscopy for FAI and labral injuries. METHODS: Patients that underwent hip arthroscopy between 2009 and 2014 were selected retrospectively. From this population, only professional soccer players competing at national level were included (Tegner 10). Arthroscopic surgery was proposed in patients with persistent pain. All patients were assessed for VAS score preoperatively and at 3, 6, 12 and 24 months post-op. HOS (sport and DLA) and mHHS tests were performed at the same time periods. RESULTS: All patients were men with a mean age of 26.5 ± 7.1 years old. Preoperative VAS (7.4 ± 1.3), HOS ADL (67.7 ± 5.5), HOS sport (37.6 ± 18.7) and mHHS (72.5 ± 8.8) showed improved scores during long-term follow-up. Time to return to play was 10.8 months (SD ± 4.3), with range between 4 and 20 months. Mean follow-up was 45.4 ± 15.6 months (range from 26 to 72 months). No differences were observed between non-active and active patients at final follow-up with respect to chondral lesions, but significant differences were observed with reference to management of the labrum (p = 0.031), where a higher rate of labrectomies existed among inactive patients and a higher rate of suture among active patients. CONCLUSIONS: Hip arthroscopy is a safe procedure with very good return to play results, but for optimized return to football one should consider patient age at the time of surgery, the condition of the labrum and low scores on the Harris Hip Score (mHHS) and HOS (sport version) as predictive factors for poor prognosis. Level of evidence IV.

CBCT uses in clinical endodontics: the effect of CBCT on the ability to locate MB2 canals in maxillary molars.

AIM: To determine whether a CBCT volume can aid in the location of MB2 canals in maxillary molars. METHODOLOGY: This prospective clinical study involved 50 patients that needed RCT on a maxillary molar. The teeth where the MB2 was located upon access with the dental operating microscope received routine root canal treatment, and teeth where MB2 was not located had a CBCT volume made after instrumenting the located canals. At the second appointment, the clinician used the aid of the CBCT volume and troughing to attempt to locate MB2. RESULTS: The clinicians located MB2 upon initial access in 70% (n = 35) of teeth. In the remaining 15 teeth, CBCT and troughing located MB2 53% of the time in that group (8/15 teeth). Overall, MB2 was located in 86% of the 50 first and second maxillary molars (maxillary first molars 90% and maxillary second molars 73%). A total of 15 CBCT volumes were made, and of these teeth, 33% of MB2 canals (5/15 teeth) were visualized on the CBCT volume. CONCLUSIONS: This prospective clinical study showed that the effectiveness of using CBCT to locate additional MB2 canals in maxillary molars appears limited. The use of the dental operating microscope in conjunction with selective troughing and CBCT imaging allowed clinicians to locate 90% (maxillary first molars) and 73% (maxillary second molars) of MB2 canals.

Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression.

Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells. Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMAIII), which accumulates in glial cells without compromising cell viability. MMAIII LD50 in astrocytes was 10.52 µM, however, exposure to sub-toxic MMAIII concentrations (50-1000 nM) significantly increased IL-1ß, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and ß-secretase (BACE-1) increased gene expression, mainly for those MMAIII concentrations that also induced TNF-α over-expression. Other effects of MMAIII on cortical astrocytes included increased proliferative and metabolic activity. All tested MMAIII concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMAIII induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.

Pharmacological targeting of histamine H4 receptor in periodontal disease.

OBJECTIVE: The objective of this study was to investigate whether histamine H4 receptor (H4 R) antagonists could prevent experimental periodontitis (EP)-induced histological, functional and inflammatory alterations in submandibular gland (SMG), periodontal bone and gingiva. METHODS: Bilateral EP was induced for 2 weeks in anaesthetized male rats. The effect of systemic and local administration of H4 R antagonists (JNJ7777120, JNJ10191584) on histopathology and functionality of SMG, bone loss and gingival inflammation was evaluated. RESULTS: The subcutaneous administration of JNJ7777120 prevented periodontitis-induced SMG histological injury, reducing vacuolization and apoptosis and additionally reversed the increased prostaglandin E2 (PGE2) levels in SMG while it partially reversed the methacholine-induced salivation reduction produced by periodontitis. JNJ7777120 attenuated bone loss and the increased PGE2 levels and inflammatory infiltration in gingival tissue of rats with periodontitis. Finally, local administration of JNJ7777120 and JNJ10191584 was also beneficial for improving periodontal parameters. CONCLUSIONS: H4 receptor antagonists are able to ameliorate periodontitis-induced injury on SMG, gingival tissue and bone structure, suggesting that pharmacological targeting of H4 R could be an attractive strategy to improve periodontal health.

Histamine reduces boron neutron capture therapy-induced mucositis in an oral precancer model.

OBJECTIVES: Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue. MATERIALS AND METHODS: Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1). RESULTS: Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs CONTROL: 55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration. CONCLUSION: Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer.

Analysis of Th1, Th17 and regulatory T cells in tuberculosis case contacts.

We have hypothesized that individuals infected with Mycobacteriumtuberculosis that exhibit different patterns of immune reactivity in serial interferon (IFN)-γ release assays (IGRA's) correspond to different status within the immune spectrum of latent tuberculosis (TB). Accordingly, we analyzed the possible association between the consistent results (negative or positive) in an IGRA test and relevant immune parameters, mainly the levels of Th1 and Th17 lymphocytes and T regulatory (Treg) cells in the peripheral blood of TB case contacts. We found that individuals with a persistently positive IGRA showed increased levels of Th1 and Th17 lymphocytes upon in vitro stimulation with MTB antigens. In addition, a significant increase in the proportion of CD4+CTLA-4+ and CD4+Foxp3+ cells was detected in assays with blood samples from these individuals. Our data support that different immune phenotypes can be identified into the spectrum of latent TB, by combining different parameters of immune reactivity against MTB.

Analysis of SIRT1 genetic variants in young Mexican individuals: relationships with overweight and obesity.

The high prevalence of obesity in Mexico starting from the early stages of life is concerning and represents a major public health problem. Genetic association studies have reported that single nucleotide variants (SNVs) in SIRT1, an NAD+-dependent deacetylase that plays an important role in the regulation of metabolic cellular functions, are associated with multiple metabolic disorders and the risk of obesity. In the present study, we analyzed the effect that the SNVs rs1467568 and rs7895833 of the SIRT1 gene may have on cardiometabolic risk factors in a young adult population from Mexico. A cross-sectional study was carried out with young adults between the ages of 18 and 25 who had a body mass index (BMI) greater than 18.5 kg/m2. This study included 1122 young adults who were classified into the normal weight (n = 731), overweight group (n = 277), and obesity group (n = 114) according to BMI of whom 405 and 404 volunteers were genotyped for rs1467568 and rs7895833 respectively using TaqMan probes through allelic discrimination assays. We found that the male sex carrying the G allele of rs7895833 had slightly lower BMI levels (p = 0.009). Furthermore, subjects carrying rs1467568 (G allele) showed a 34% lower probability of presenting with hyperbetalipoproteinemia where female carrying rs1467568 had lower levels of total cholesterol (p = 0.030), triglycerides (p = 0.026) and LDL cholesterol (p = 0.013). In conclusion, these findings suggest that the presence of both SNVs could have a non-risk effect against dyslipidemia in the Mexican population.

Celiac disease.

Celiac disease, with a prevalence around 1% of the general population, is the most common genetically-induced food intolerance in the world. Triggered by the ingestion of gluten in genetically predisposed individuals, this enteropathy may appear at any age, and is characterized by a wide variety of clinical signs and symptoms. Among them, gastrointestinal presentations include chronic diarrhea, abdominal pain, weight loss or failure to thrive in children; but extra-intestinal manifestations are also common, and actually appear to be on the rise. They include a large variety of ailments, such as dermatitis Herpetiformis, anemia, short stature, osteoporosis, arthritis, neurologic problems, unexplained elevation of transaminases, and even female infertility. For the clinician interested in oral diseases, celiac disease can lead to delayed tooth eruption, dental enamel hypoplasia, recurrent oral aphthae. Diagnosing celiac disease requires therefore a high degree of suspicion followed by a very sensitive screening test: serum levels of the autoantibody anti-tissue transglutaminase. A positive subject will then be confirmed by an intestinal biopsy, and will then be put on a strict gluten-free diet, that in most cases will bring a marked improvement of symptoms. Newer forms of treatment which in the future will probably be available to the non-responsive patients are currently being actively pursued.

Sodium Selenite Diminished the Regulatory T Cell Differentiation In Vitro.

Sodium selenite modulates the activity of lymphocytes. It negatively regulates the suppressive activity of cells and increases the immune response. In this study, we evaluated whether the regulatory T cell differentiation was modulated by sodium selenite. The percentages of CD4+CD25+Foxp3+, CD4+CD25+, and CD4+CTLA-4+ cells in CD4+ T cells cultures stimulated with IL-2 and TGF-ß in the presence or absence of selenium, in the form of sodium selenite (2.0×10-6M), were evaluated by flow cytometry. The mRNA expression of TET2/3 enzymes and IL-10 was analyzed by RT-qPCR and the levels of IL-10 were measured by an ELISA. We observed a decrease in CD4+CD25+Foxp3+ and CD4+CTLA-4+ cells in presence of selenium. However, normal percentages were reached again after selenium removal. An increase in CD4+CTL4-4+ cells was detected in selenium-primed cell cultures in absence of IL-2 and TGF-ß. In addition, we observed a decrease in TET3 in presence of selenium. Finally, we observed an augment in IL-10 transcription and protein levels and relative expression of TET2 in cultures exposed to selenium. We suggest that selenium reversibly affects the regulatory T cell differentiation in vitro. Likewise, selenium may modulate Treg percentages promoting optimal immune responses and, at the same time, the expression of specific suppressor molecules.

Phase I combination study of trabectedin and capecitabine in patients with advanced malignancies.

BACKGROUND: To determine the maximum tolerated dose (MTD), safety and pharmacokinetics of trabectedin with capecitabine in patients with advanced malignancies. DESIGN: In this Phase I, open-label, dose-finding study, patients refractory to standard therapy received trabectedin (3-h intravenous infusion, 0.4-1.3 mg/m(2), day 1) and capecitabine (2,000 or 1,600 mg/m(2)/day orally, days 2-15) every 3 weeks. Standard "3 + 3" dose escalation was used to define the MTD. Antitumor response was assessed every two cycles; adverse events (AEs) were recorded throughout. RESULTS: Forty patients received 149 cycles of treatment (median 2; range 1-11) at nine dose levels. Gastrointestinal dose-limiting toxicities in two patients at two dose levels with capecitabine at 2,000 mg/m(2)/day prompted dose reduction to 1,600 mg/m(2)/day and initiation of new trabectedin dose escalation at 0.6 mg/m(2). The MTD was capecitabine 1,600 mg/m(2)/day + trabectedin 1.1 mg/m(2). Common grade 3-4 drug-related AEs were neutropenia (20%), nausea (18%), diarrhea (15%) and palmar-plantar erythrodysesthesia (15%). One patient with cholangiocarcinoma achieved a sustained partial response, and 18 patients maintained stable disease (six for ≥6 months). CONCLUSIONS: The combination of trabectedin and capecitabine is generally well tolerated, without pharmacokinetic interactions, and shows some activity in patients with advanced cancers.

AIM2-inflammasome role in systemic lupus erythematous and rheumatoid arthritis.

The inflammasome AIM2 regulates multiple aspects of innate immune functions and serves as a critical mediator of inflammatory responses. AIM2 inflammasome activation leads to the production of pro-inflammatory cytokines, IL-1ß and IL-18 and participates triggering a pyroptosis response needed to counteract excessive cell proliferation. In addition, AIM2 expression and activation is wide regulated since alteration in its activity may derived in pathological consequences. Consequently, deregulated AIM2 activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of AIM2 inflammasome, as well as its contribution in rheumatoid arthritis and systemic lupus erythematous pathology. Finally, we highlight the participation of the AIM2-inflammasome at the level of joint in rheumatoid arthritis and at kidney in systemic lupus erythematous. The development of therapeutic strategies based on modulation of AIM2-inflammasome activity should have a tissue-specific focus.

[Association between influenza vaccination and mortality due to COVID-19]. / Asociación entre la vacunación contra influenza y la mortalidad por COVID-19.

Background: It has recently been suggested that influenza vaccination may be a factor associated with decreased COVID-19 mortality. Methods: An age-matched case-control study based on hospital cases. We included subjects aged 18 years and older with a diagnosis of moderate to severe COVID-19. Infection was corroborated by RT-PCR test for SARS-COV-2. Deceased subjects were considered cases, controls were patients discharged due to improvement of acute symptoms. We used bivariate analysis to determine factors associated with death from COVID-19, and calculated odds ratios and 95% confidence intervals. Results: A total of 560 patients were included in the study, 214 (38.2%) were considered cases and 346 (61.7%) controls. A significant difference was observed with the presence of type 2 diabetes mellitus [54% vs. 39.3% between cases and controls, respectively (p=.04)] and having received influenza vaccination (p= .02). Type 2 diabetes mellitus was associated with higher COVID-19 mortality [OR 1.8 (95% CI 1.2-2.5) p=.01], whereas having been immunised against influenza in 2019 was associated with lower mortality in this group of patients [OR .6 (95% CI .4-.9) p=.02]. Conclusions: Influenza vaccination in the previous year appears to be associated with lower mortality from COVID-19; whereas type 2 diabetes mellitus is confirmed as a condition associated with higher mortality.

Gingival Thickness and Outcome of Periodontal Plastic Surgery Procedures: A Meta-regression Analysis.

OBJECTIVE: To evaluate the impact of soft tissue thickness (STT) on root coverage achieved with different periodontal plastic surgery procedures. BACKGROUND: Gingival recession has been managed successfully through various surgical approaches, with great variability in outcomes. Anatomic characteristics of the recipient site and selected technique account in part for this variability. Gingival flap thickness is one of the most critical site-related characteristics. METHODS: An electronic search was conducted on the major databases (PubMed, Embase, Web of Science). Human prospective studies with at least 6 mo of follow-up and with a numeric baseline measurement for gingival thickness were eligible. Only studies including nonsmoking patients were considered. Variables included surgical approach, participant characteristics, local anatomic factors, and follow-up time. Primary outcome was mean percentage root coverage (%RC) achieved, and complete root coverage was a secondary outcome. RESULTS: A total of 42 studies were included (35 randomized controlled trials, 5 case series, 1 prospective cohort study, and 1 controlled clinical trial). Across studies, the pooled %RC was 81.9% (95% CI, 79.1% to 84.7%). The %RC was not significantly associated (P = 0.267) with baseline soft tissue thickness; however there was a significant (P = 0.031) inverse relationship between STT and %RC after 12-mo follow-up. Subgroup analysis showed that for no graft, there was a significant (P = 0.025) positive relationship between STT and %RC with the exclusion of the single outlier study based on STT. CONCLUSIONS: STT plays a limited role in predicting root coverage across all approaches; when flaps are performed with no graft, the effect of STT is most critical. The length of time following surgery appears to influence outcomes, with 12-mo follow-up offering greater insight. KNOWLEDGE TRANSFER STATEMENT: The results of this study can suggest to clinicians which periodontal plastic surgery technique to employ when treating challenging cases. In particular, it can be helpful when selecting the treatment approach to treat thin phenotype sites. This study could help clinicians provide a more appropriate treatment decision in such cases.

B regulatory cells associated with changes in biochemical and inflammatory parameters in normal-glycemic individuals, pre-diabetes and T2DM patients.

AIM: To determine the percentages of (CD19 + CD24 + CD38+, CD19 + CD24 + CD27+, CD19 + IL-10+)-Breg cells, IL-17 single and IL-17+/IFN-γ double producers T cells and IFN-γ+ T cells, in normal-glycemic individuals, prediabetes and T2DM patients, and to analyze the association of Breg cells with metabolic parameters of T2DM. METHODS: percentages of Breg cells, IL-17+ and IL-17 + IFN-γ+ T cells, IFN-γ+ T cells and IL-10 were determined by flow cytometry. IL-6 levels were evaluated by ELISA assay. RESULTS: increased IL-6 levels, IL-17+ and IL-17 + IFN-γ+ T cells and a diminution of IL-10 levels and CD19 + IL-10+ cells in T2DM patients were observed. We found that CD19 + CD24 + CD27+ cells and CD19 + CD24 + CD38+ cells were increased in T2DM patients. The percentages of CD19 + CD24 + CD38+ cells were associated with HOMA-B, TyG index, HDL and cholesterol values. In normal-glycemic individuals, CD19 + CD24 + CD27+ cells were inversely associated to triglycerides and TyG index. In prediabetes patients, CD19 + CD24 + CD38+ cells were inversely related with cholesterol and LDL. Finally, CD19 + CD24 + CD38+ cells were inversely related with HDL values in T2DM patients. CONCLUSION: Our results suggest that increased percentages of IL-17 single and IL-17/IFN-γ double producers T cells in T2DM patients may be a consequence of the initial CD19 + IL-10+ cells reduction. Furthermore, dyslipidemia could play an important role in percentages and activity of B regulatory cells.

Immunoglobulin synthesis in mice: suppression by anti-allotype antibody.

In the mouse, antibody directed against an immunoglobulin allotype, Ig-1b, passed from mother to offspring or injected into neonates, suppresses synthesis of immunoglobulin carrying Ig-1b. In allotype homozygotes as well as heterozygotes the allotype suppression is manifested both by a delay of several weeks in attaining initial detectable allotype levels and a reduction in allotype level continuing into adulthood. A possible mechanism for the differentiation of the immune system consistent with both the kinetics of suppression reported here for the mouse and the comparatively longer lived and more complete allotype suppression described for the rabbit is discussed. Evidence for a strong intralitter (as opposed to interlitter) correlation of age of onset of immunoglobulin allotype synthesis is presented.

Opsin co-expression in Limulus photoreceptors: differential regulation by light and a circadian clock.

A long-standing concept in vision science has held that a single photoreceptor expresses a single type of opsin, the protein component of visual pigment. However, the number of examples in the literature of photoreceptors from vertebrates and invertebrates that break this rule is increasing. Here, we describe a newly discovered Limulus opsin, Limulus opsin5, which is significantly different from previously characterized Limulus opsins, opsins1 and 2. We show that opsin5 is co-expressed with opsins1 and 2 in Limulus lateral and ventral eye photoreceptors and provide the first evidence that the expression of co-expressed opsins can be differentially regulated. We show that the relative levels of opsin5 and opsin1 and 2 in the rhabdom change with a diurnal rhythm and that their relative levels are also influenced by the animal's central circadian clock. An analysis of the sequence of opsin5 suggests it is sensitive to visible light (400-700 nm) but that its spectral properties may be different from that of opsins1 and 2. Changes in the relative levels of these opsins may underlie some of the dramatic day-night changes in Limulus photoreceptor function and may produce a diurnal change in their spectral sensitivity.