Life Sciences Commons^™

Prenatal Cocaine Exposure Alters Alpha2 Receptor Expression In Adolescent Rats, Rosemarie M. Booze, David R. Wallace, Janelle M. Silvers, Barbara J. Strupp, Diane M. Snow, Charles F. Mactutus

Neuroscience Faculty Publications

BACKGROUND: Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE) in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured alpha2-adrenergic receptor (alpha2-AR) density in adolescent (35-days-old) rats, using [3H]RX821002 (5 nM).

RESULTS: Sex-specific alterations of alpha2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of alpha2-AR in parietal cortex.

CONCLUSION: These data suggest that prenatal cocaine exposure results in a persistent alteration …

Type 3 Deiodinase Is Critical For The Maturation And Function Of The Thyroid Axis, Arturo Hernandez, M. Elena Martinez, Steven Flering, Valerie Anne Galton, Donald St. German

Dartmouth Scholarship

Developmental exposure to appropriate levels of thyroid hormones (THs) in a timely manner is critical to normal development in vertebrates. Among the factors potentially affecting perinatal exposure of tissues to THs is type 3 deiodinase (D3). This enzyme degrades THs and is highly expressed in the pregnant uterus, placenta, and fetal and neonatal tissues. To determine the physiological role of D3, we have generated a mouse D3 knockout model (D3KO) by a targeted inactivating mutation of the Dio3 gene in mouse ES cells. Early in life, D3KO mice exhibit delayed 3,5,3′-triiodothyronine (T3) clearance, a markedly elevated serum T3 level, and …

Effects Of Lesions Of The Bed Nucleus Of The Stria Terminalis, Laterual Hypothalamus, Or Insular Cortex On Conditioned Taste Aversion And Conditioned Odor Aversion, Christopher T. Roman, Nino Nebieridze, Aristides Sastre, Steve Reilly

Scholarship and Professional Work – COPHS

The effects of permanent forebrain lesions on conditioned taste aversions (CTAs) and conditioned odor aversions (COAs) were examined in 3 experiments. In Experiment 1, lesions of the bed nucleus of the stria terminalis had no influence on CTA or COA acquisition. Although lesions of the lateral hypothalamus induced severe hypodipsia in Experiment 2, they did not prevent the acquisition of CTAs or COAs. Finally, in Experiment 3, lesions of the insular cortex retarded CTA acquisition but had no influence on COA acquisition. The implications of these findings are discussed with regard to the forebrain influence on parabrachial nucleus function during …

Differential Habituation Of Male Betta Splendens To Qualitatively Different Stimuli, Lauren Baard

Undergraduate Research Symposium (UGRS)

Habituation is a learning mechanism that functions to decrease the amount of energy and attention focused on a certain stimuli. Male Siamese Fighting Fish, Betta splendens, are territorial animals that defend their territories using a number of aggressive displays. Male Bettas have previously shown the ability to habituate to the presence of a conspecific male when visually exposed to each other. Due to the costly nature of many of the male Betta’s displays, I hypothesized that male Bettas should differentially habituate to qualitatively different stimuli. I presented each of three groups of male Betta splendens with a different stimulus, each …

Visibility, Visual Awareness, And Visual Masking Of Simple Unattended Targets Are Confined To Areas In The Occipital Cortex Beyond Human V1/V2, Peter U. Tse, Susanna Martinez-Conde, Alexander A. Schlegel, Stephen L. Macknik

Dartmouth Scholarship

In visual masking, visible targets are rendered invisible by modifying the context in which they are presented, but not by modifying the targets themselves. Here, we localize the neuronal correlates of visual awareness in the human brain by using visual masking illusions. We compare monoptic visual masking activation, which we find within all retinotopic visual areas, with dichoptic masking activation, which we find only in those retinotopic areas downstream of V2. Because monoptic and dichoptic masking are equivalent in magnitude perceptually, the present results establish a lower bound for maintenance of visual awareness of simple unattended targets. Moreover, we find …

Cortical Regions Associated With Autonomic Cardiovascular Regulation During Lower Body Negative Pressure In Humans., Derek S Kimmerly, Deborah D O'Leary, Ravi S Menon, Joseph S Gati, J Kevin Shoemaker

Kinesiology Publications

The purpose of the present study was to determine the cortical structures involved with integrated baroreceptor-mediated modulation of autonomic cardiovascular function in conscious humans independent of changes in arterial blood pressure. We assessed the brain regions associated with lower body negative pressure (LBNP)-induced baroreflex control using functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast in eight healthy male volunteer subjects. The levels of LBNP administered were 5, 15 and 35 mmHg. Heart rate (HR; representing the cardiovascular response) and LBNP (representing the baroreceptor activation level) were simultaneously monitored during the scanning period. In addition, estimated central venous pressure …

Ecological Costs And Benefits Of Defenses In Nectar, Lynn S. Adler, Rebecca E. Irwin

Dartmouth Scholarship

The nectar of many plant species contains defensive compounds that have been hypothesized to benefit plants through a variety of mechanisms. However, the relationship between nectar defenses and plant fitness has not been established for any species. We experimentally manipulated gelsemine, the principal alkaloid of Carolina jessamine (Gelsemium sempervirens), in nectar to determine its effect on pollinator visitation, nectar robber visitation, and male and female plant reproduction. We found that nectar robbers and most pollinators probed fewer flowers and spent less time per flower on plants with high compared to low nectar alkaloids. High alkaloids decreased the donation of fluorescent …

Fatigue Resistance Of Rat Extraocular Muscles Does Not Depend On Creatine Kinase Activity, Colleen A. Mcmullen, Katrin Hayeß, Francisco H. Andrade

Physiology Faculty Publications

BACKGROUND: Creatine kinase (CK) links phosphocreatine, an energy storage system, to cellular ATPases. CK activity serves as a temporal and spatial buffer for ATP content, particularly in fast-twitch skeletal muscles. The extraocular muscles are notoriously fast and active, suggesting the need for efficient ATP buffering. This study tested the hypotheses that (1) CK isoform expression and activity in rat extraocular muscles would be higher, and (2) the resistance of these muscles to fatigue would depend on CK activity.

RESULTS: We found that mRNA and protein levels for cytosolic and mitochondrial CK isoforms were lower in the extraocular muscles than in …

Donepezil Effects On Mood In Patients With Schizophrenia And Schizoaffective Disorder, S Craig Risch, Michael D. Horner, Susan R. Mcgurk, Simmy Palecko, John S. Markowitz, Ziad Nahas, C. Lindsay Devane

Dartmouth Scholarship

Donepezil, 5 mg/d for 6 wk then 10 mg/d for 6 wk, and placebo daily for 12 wk in a double-blind cross-over paradigm, was added to the therapeutic regimen of 13 patients with schizophrenia or schizoaffective disorders, clinically stable on atypical antipsychotic medications. Patients had varying degrees of depressive symptoms, ranging from no depression to clinically significant depression. There was no worsening or induction of depression in individual patients or the group as a whole. In addition there was a statistically significant antidepressant effect in the group as a whole during the donepezil condition and a clinically significant antidepressant effect …

Manganese Distribution Across The Blood-Brain Barrier. Iv. Evidence For Brain Influx Through Store-Operated Calcium Channels, Janelle S. Crossgrove, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is a required co-factor for many ubiquitous enzymes; however, chronic Mn overexposure can cause manganism, a parkinsonian-like syndrome. Previous studies showed Mn influx into brain is carrier-mediated, though the putative carrier(s) were not established. Studies conducted with cultured bovine brain microvascular endothelial cells (bBMECs), which comprise the blood–brain barrier, revealed ⁵⁴Mn (II) uptake positively correlated with pH, was temperature-dependent, and was sodium- and energy-independent. Brain ⁵⁴Mn uptake correlated inversely with calcium (Ca) concentration, but ⁴⁵Ca uptake was unaltered by high Mn concentration. Lanthanum (La), a non-selective inhibitor of several Ca channel types, as well as …

Predicting Childhood Sexual Or Physical Abuse: A Logistic Regression Geo-Mapping Approach To Prevention, Roland K. Tadoum, Kamila Smolij, Michelle A. Lyn, Craig W. Johnson

Faculty, Staff and Student Publications

This study investigates the degree to which gender, ethnicity, relationship to perpetrator, and geomapped socio-economic factors significantly predict the incidence of childhood sexual abuse, physical abuse and non- abuse. These variables are then linked to geographic identifiers using geographic information system (GIS) technology to develop a geo-mapping framework for child sexual and physical abuse prevention.

The Caenorhabditis Elegans F-Box Protein Sel-10 Promotes Female Development And May Target Fem-1 And Fem-3 For Degradation By The Proteasome, Sibylle Jager, Hillel T. Schwartz, H. Robert Horvitz, Barbara Conradt

Dartmouth Scholarship

The Caenorhabditis elegans F-box protein SEL-10 and its human homolog have been proposed to regulate LIN-12 Notch signaling by targeting for ubiquitin-mediated proteasomal degradation LIN-12 Notch proteins and SEL-12 PS1 presenilins, the latter of which have been implicated in Alzheimer's disease. We found that sel-10 is the same gene as egl-41, which previously had been defined by gain-of-function mutations that semidominantly cause masculinization of the hermaphrodite soma. Our results demonstrate that mutations causing loss-of-function of sel-10 also have masculinizing activity, indicating that sel-10 functions to promote female development. Genetically, sel-10 acts upstream of the genes fem-1, fem-2, and fem-3 and …

The Cohesion Protein Ord Is Required For Homologue Bias During Meiotic Recombination, Hayley A. Webber, Louisa Howard, Sharon E. Bickel

Dartmouth Scholarship

During meiosis, sister chromatid cohesion is required for normal levels of homologous recombination, although how cohesion regulates exchange is not understood. Null mutations in orientation disruptor (ord) ablate arm and centromeric cohesion during Drosophila meiosis and severely reduce homologous crossovers in mutant oocytes. We show that ORD protein localizes along oocyte chromosomes during the stages in which recombination occurs. Although synaptonemal complex (SC) components initially associate with synapsed homologues in ord mutants, their localization is severely disrupted during pachytene progression, and normal tripartite SC is not visible by electron microscopy. In ord germaria, meiotic double strand breaks appear …

Ec04-469 When Words Are Used As Weapons: The Signs Of Verbal Abuse (Part 2 Of A Four Part Series), Kathy Bosch

University of Nebraska-Lincoln Extension: Historical Materials

Verbal abuse finally is being recognized as a form of domestic violence and as the behavior that usually precedes physical violence. There has been little support for individuals who are verbally abused because it's not as readily visible as a black eye or bruise. However, many individuals, particularly women, suffer with verbal assaults from their partners.

Ec04-464 There's No Excuse For Abuse (Part 1 Of A Four Part Series), Kathy Bosch

University of Nebraska-Lincoln Extension: Historical Materials

In this series of four articles, information will be provided from the Family Violence Prevention Fund, the Nebraska and Kansas Coalitions Against Sexual and Domestic Violence, K-State Research and Extension, Nebraska Cooperative Extension, and many other research-based sources. You will learn more about how you can help a woman who is being abused, how you can offer support to children in abusive situations, how you may approach potential abusers, how to access resources, steps that can be taken in the workplace to help end domestic violence, what to teach children about partner abuse, how to raise community awareness, and how …

Ec04-465 There's No Excuse For Abuse: Men Can Help Stop Domestic Violence (Part 2 Of A Four Part Series), Kathy Bosch

University of Nebraska-Lincoln Extension: Historical Materials

One of the hardest things to do is to confront a family member, friend, co-worker, or neighbor who abuses his wife or girlfriend about his inexcusable and wrongful behavior. You may feel that you don't know what to say, are fearful of becoming involved, or that his behavior towards his significant other is none of your business.

Your friend may want to talk about the problem but has not had the opportunity because no one has had the courage to address the issue with him. Your friend may hesitate to talk about his behavior but at least you can let …

Ec04-470 When Words Are Used As Weapons: What Can I Do? (Part 3 Of A Four Part Series), Kathy Bosch

University of Nebraska-Lincoln Extension: Historical Materials

In the midst of conflict, it's sometimes difficult to determine if the argument is hostile or actually a misunderstanding. However, according to Elaine Johannes, Kansas State University Extension family and community mental health specialist, if the conflict intentionally humiliates, degrades, belittles or antagonizes, there is no confusion whether or not the conflict comes from conversational style differences; it's definitely abuse.

One theory that examines the lack of understanding between women and men is attributed to gender differences in the ways they speak. Problems may exist when couples ignore these differences in conversational styles. The differences are neither good or bad, …

Genetic Polymorphisms Of The Interleukin-1 Gene And Early Marginal Bone Loss Around Endosseous Dental Implants, Hitomi Shimpuku, Yasuhiro Nosaka, Tatsuya Kawamura, Yoichi Tachi, Mitsuko Shinohara, Kiyoshi Ohura

Faculty, Staff and Student Publications

Dental implant surgery commonly proceeds in two stages. It is generally accepted that bone loss around implants does not occur at stage-II surgery because implants do not receive mechanical loading. However, early marginal bone loss around implants occasionally does occur during the healing period. Genetic polymorphisms in the interleukin-1 (IL-1) gene have been reported to be important for bone homeostasis and susceptibility to bone disease. We therefore investigated whether the idiopathic early marginal bone loss around implants is related to polymorphisms in the IL-1 gene. We performed a case-control study. Patients demonstrating marginal bone loss around implants at stage-II surgery …

Distinct Neural Systems Subserve Person And Object Knowledge, Jason P. Mitchell, Todd F. Heatherton, C. Neil Macrae

Dartmouth Scholarship

Studies using functional neuroimaging and patient populations have demonstrated that distinct brain regions subserve semantic knowledge for different classes of inanimate objects (e.g., tools, musical instruments, and houses). What this work has yet to consider, however, is how conceptual knowledge about people may be organized in the brain. In particular, is there a distinct functional neuroanatomy associated with person knowledge? By using event-related functional magnetic resonance imaging (fMRI), we measured neural activity while participants made semantic judgments about people or objects. A unique pattern of brain activity was associated with person judgments and included brain regions previously implicated in other …

Meiotic Cohesion Requires Accumulation Of Ord On Chromosomes Before Condensation, Eric M. Balicky, Matthew W. Endres, Cary Lai, Sharon E. Bickel

Dartmouth Scholarship

Cohesion between sister chromatids is a prerequisite for accurate chromosome segregation during mitosis and meiosis. To allow chromosome condensation during prophase, the connections that hold sister chromatids together must be maintained but still permit extensive chromatin compaction. In Drosophila, null mutations in the orientation disruptor (ord) gene lead to meiotic nondisjunction in males and females because cohesion is absent by the time that sister kinetochores make stable microtubule attachments. We provide evidence that ORD is concentrated within the extrachromosomal domains of the nuclei ofDrosophila primary spermatocytes during early G2, but accumulates on the meiotic chromosomes by …

Tanaidacea (Crustacea: Peracardia) Of The Gulf Of Mexico. X. The Question Of Being Male, Kim Larsen

Gulf and Caribbean Research

Three new species Parafilitanais mexicana, Collettea elongata, and Paragathotanais medius are described from deep-sea localities in the Gulf of Mexico. The male of Parafilitanais does not vary conspicuously from the female, except for possessing pleopods. Male Paragathotanais reveal that the mouthparts display some degree of sexual dimorphism. Males of all 3 species possess functional mouthparts. The problems identifying male Tanaidacea are discussed. The number of terminal spiniform setae on the maxillule is considered invalid as a diagnostic character. Keys to the species of Parafilitanais and Paragathotanais are given.

Critical Analysis Of Cerebrovascular Autoregulation During Repeated Head-Up Tilt., R L Hughson, M R Edwards, D D O'Leary, J K Shoemaker

Kinesiology Publications

BACKGROUND AND PURPOSE: Cerebrovascular autoregulation has been described with a phase lead of cerebral blood flow preceding changes in cerebral perfusion pressure (CPP), but there has been less focus on the effect of CPP on cerebral vascular resistance. We investigated these relations during spontaneous fluctuations (control) and repeated head-up tilt.

METHODS: Eight healthy adults were studied in supine rest and repeated tilt with 10-second supine, 10 seconds at 45 degrees head-up tilt for a total of 12 cycles. Cerebral blood flow was estimated from mean flow velocity (MFV) by transcranial Doppler ultrasound, CPP was estimated from corrected finger pressure (CPP(F)), …

Cakß/Pyk2 Kinase Is A Signaling Link For Induction Of Long-Term Potentiation In Ca1 Hippocampus, Yueqiao Huang, Wei-Yang Lu, Declan W. Ali, Kenneth A. Pelkey, Graham M. Pitcher, You Ming Lu, Hiroshi Aoto, John C. Roder, Terukatsu Sasaki, Michael W. Salter

PCOM Scholarly Works

Long-term potentiation (LTP) is an activity-dependent enhancement of synaptic efficacy, considered a model of learning and memory. The biochemical cascade producing LTP requires activation of Src, which upregulates the function of NMDA receptors (NMDARs), but how Src becomes activated is unknown. Here, we show that the focal adhesion kinase CAKß/Pyk2 upregulated NMDAR function by activating Src in CA1 hippocampal neurons. Induction of LTP was prevented by blocking CAKß/Pyk2, and administering CAKß/Pyk2 intracellularly mimicked and occluded LTP. Tyrosine phosphorylation of CAKß/Pyk2 and its association with Src was increased by stimulation that produced LTP. Finally, CAKß/Pyk2-stimulated enhancement of synaptic AMPA responses was …

Impaired Fast-Spiking, Suppressed Cortical Inhibition, And Increased Susceptibility To Seizures In Mice Lacking Kv3.2 K+ Channel Proteins, David Lau, Eleazar Vega-Saenz De Miera, Diego Contreras, Alan Chow, Richard Paylor, Christopher S. Leonard, Bernardo Rudy

NYMC Faculty Publications

Voltage-gated K(+) channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to -10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one …

Prolonged Cyclooxygenase-2 Induction In Neurons And Glia Following Traumatic Brain Injury In The Rat, Kenneth I. Strauss, Mary F. Barbe, Renee Marshall Demarest, Ramesh Raghupathi, Samir Mehta, Raj K. Narayan

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Cyclooxygenase-2 (COX2) is a primary inflammatory mediator that converts arachidonic acid into precursors of vasoactive prostaglandins, producing reactive oxygen species in the process. Under normal conditions COX2 is not detectable, except at low abundance in the brain. This study demonstrates a distinctive pattern of COX2 increases in the brain over time following traumatic brain injury (TBI). Quantitative lysate ribonuclease protection assays indicate acute and sustained increases in COX2 mRNA in two rat models of TBI. In the lateral fluid percussion model, COX2 mRNA is significantly elevated (>twofold, p < 0.05, Dunnett) at 1 day postinjury in the injured cortex and bilaterally in the hippocampus, compared to sham-injured controls. In the lateral cortical impact model (LCI), COX2 mRNA peaks around 6 h postinjury in the ipsilateral cerebral cortex (fivefold induction, p < 0.05, Dunnett) and in the ipsilateral and contralateral hippocampus (two- and six-fold induction, respectively, p < 0.05, Dunnett). Increases are sustained out to 3 days postinjury in the injured cortex in both models. Further analyses use the LCI model to evaluate COX2 induction. Immunoblot analyses confirm increased levels of COX2 protein in the cortex and hippocampus. Profound increases in COX2 protein are observed in the cortex at 1-3 days, that return to sham levels by 7 days postinjury (p < 0.05, Dunnett). The cellular pattern of COX2 induction following TBI has been characterized using immunohistochemistry. COX2-immunoreactivity (-ir) rises acutely (cell numbers and intensity) and remains elevated for several days following TBI. Increases in COX2-ir colocalize with neurons (MAP2-ir) and glia (GFAP-ir). Increases in COX2-ir are observed in cerebral cortex and hippocampus, ipsilateral and contralateral to injury as early as 2 h postinjury. Neurons in the ipsilateral parietal, perirhinal and piriform cortex become intensely COX2-ir from 2 h to at least 3 days postinjury. In agreement with the mRNA and immunoblot results, COX2-ir appears greatest in the contralateral hippocampus. Hippocampal COX2-ir progresses from the pyramidal cell layer of the CA1 and CA2 region at 2 h, to the CA3 pyramidal cells and dentate polymorphic and granule cell layers by 24 h postinjury. These increases are distinct from those observed following inflammatory challenge, and correspond to brain areas previously identified with the neurological and cognitive deficits associated with TBI. While COX2 induction following TBI may result in selective beneficial responses, chronic COX2 production may contribute to free radical mediated cellular damage, vascular dysfunction, and alterations in cellular metabolism. These may cause secondary injuries to the brain that promote neuropathology and worsen behavioral outcome.

Mri Measures Of Middle Cerebral Artery Diameter In Conscious Humans During Simulated Orthostasis., J M Serrador, P A Picot, B K Rutt, J K Shoemaker, R L Bondar

Kinesiology Publications

BACKGROUND AND PURPOSE: The relationship between middle cerebral artery (MCA) flow velocity (CFV) and cerebral blood flow (CBF) is uncertain because of unknown vessel diameter response to physiological stimuli. The purpose of this study was to directly examine the effect of a simulated orthostatic stress (lower body negative pressure [LBNP]) as well as increased or decreased end-tidal carbon dioxide partial pressure (P(ET)CO(2)) on MCA diameter and CFV.

METHODS: Twelve subjects participated in a CO(2) manipulation protocol and/or an LBNP protocol. In the CO(2) manipulation protocol, subjects breathed room air (normocapnia) or 6% inspired CO(2) (hypercapnia), or they hyperventilated to approximately …

The Effects Of Free Fatty Acids On Gluconeogenesis And Glycogenolysis In Normal Subjects, X Chen, N Iqbal, G Boden

Rowan-Virtua School of Osteopathic Medicine Departmental Research

We have quantitatively determined gluconeogenesis (GNG) from all precursors, using a novel method employing 2H20 to address the question of whether changes in plasma free fatty acids (FFA) affect GNG in healthy, nonobese subjects. In the first study (n = 6), plasma FFA were lowered at 16 to 20 hours with nicotinic acid (NA) and were then allowed to rise at 20 to 24 hours (FFA rebound after administration of NA). FFA decreased from 387 microM at 16 hours to 43 microM at 20 hours, and then rebounded to 1,823 microM at 24 hours. GNG decreased from 58.1% at 16 …

Pharmacology Of Male Contraceptives(เภสัชวิทยาของยาคุมกำเนิดเพศชาย), Srisombat Nawanopparatsakut

The Thai Journal of Pharmaceutical Sciences

Nowadays male contraceptives begin to play an important role. However, the information about drugs that have pharmacological activity as male contraceptives is still limited. Male contraceptive drugs should be safe and provide only short-term effect. Mal...

Scanning Electron Microscopy Of The Accessory Sex Glands Of The Adult Male Rat, R. Wahlqvist, E. Dahl, K. J. Tveter

Scanning Microscopy

This study describes the morphology of the accessory sex glands of the adult male rat as observed by scanning electron microscopy (SEM). The purpose was to obtain a systematic and comparative SEM description of these glands and to evaluate different preparation techniques. A common morphological feature is polyhedral delineation of the cells, which exhibited a variable convexity of their apical surface. The cell apices were more or less studded with microvilli. Nevertheless, it was possible to distinguish the glands by their surface morphology. In the ventral prostate, there was a considerable heterogeneity in cell surface appearance. The lateral lobe bad …

Pancreatic Expression Of Interleukin-4 Abrogates Insulitis And Autoimmune Diabetes In Nonobese Diabetic (Nod) Mice., Regula Mueller, Troy Krahl, Nora Sarvetnick

Journal Articles: Regenerative Medicine

Diabetes in nonobese diabetic (NOD) mice is a T cell-dependent autoimmune disease. The destructive activities of autoreactive T cells have been shown to be tightly regulated by effector molecules. In particular, T helper (Th) 1 cytokines have been linked to diabetes pathogenesis, whereas Th2 cytokines and the cells that release them have been postulated to be protective from disease. To test this hypothesis, we generated transgenic NOD mice that express interleukin (IL) 4 in their pancreatic beta cells under the control of the human insulin promoter. We found that transgenic NOD-IL-4 mice, both females and males, were completely protected from …