Correlates of PrEP Uptake Among Young Sexual Minority Men and Transgender Women in New York City: The Need to Reframe "Risk" Messaging and Normalize Preventative Health.

Pre-exposure prophylaxis (PrEP) is an effective form of HIV prevention, but young sexual minority men face myriad barriers to PrEP uptake. Participants (n = 202) completed a survey on healthcare experiences and beliefs about HIV and PrEP. While 98% of the sample knew about PrEP, only 23.2% reported currently taking PrEP. Participants were more likely to be taking PrEP if they received PrEP information from a healthcare provider and endorsed STI-related risk compensation. Conversely, PrEP uptake was less likely among those with concerns about medication use and adherence. While there were no racial/ethnic differences in PrEP uptake, there were differences in correlates of PrEP use for White participants and participants of color. To facilitate PrEP uptake, clinicians should provide PrEP education and screen all patients for PrEP candidacy. Additionally, public health messaging must reframe HIV "risk", highlight benefits of STI testing, and emphasize the importance of preventive healthcare for SMM.

Myxoma Virus M083 Is a Virulence Factor Which Mediates Systemic Dissemination.

Poxviruses are large, DNA viruses whose protein capsid is surrounded by one or more lipid envelopes. Embedded into these lipid envelopes are three conserved viral proteins which are thought to mediate binding of virions to target cells. While the function of these proteins has been studied in vitro, their specific roles during the pathogenesis of poxviral disease remain largely unclear. Here we present data demonstrating that the putative chondroitin binding protein M083 from the leporipoxvirus myxoma virus is a significant virulence factor during infection of susceptible Oryctolagus rabbits. Removal of M083 results in a reduced capacity of virus to spread beyond the regional lymph nodes and completely eliminates infection-mediated mortality. In vitro, removal of M083 results in only minor intracellular replication defects but causes a significant reduction in the ability of myxoma virus to spread from infected epithelial cells onto primary lymphocytes. We hypothesize that the physiological role of M083 is therefore to mediate the spread of myxoma virus onto rabbit lymphocytes, allowing these cells to disseminate virus throughout infected rabbits.IMPORTANCE Poxviruses represent both a class of human pathogens and potential therapeutic agents for the treatment of human malignancy. Understanding the basic biology of these agents is therefore significant to human health in a variety of ways. While the mechanisms mediating poxviral binding have been well studied in vitro, how these mechanisms impact poxviral pathogenesis in vivo remains unclear. The current study advances our understanding of how poxviral binding impacts viral pathogenesis by demonstrating that the putative chondroitin binding protein M083 plays a critical role during the pathogenesis of myxoma virus in susceptible Oryctolagus rabbits by impacting viral dissemination through changes in the transfer of virions onto primary splenocytes.

Effect of maternal nutrient restriction on expression of glucose transporters (SLC2A4 and SLC2A1) and insulin signaling in skeletal muscle of SGA and Non-SGA sheep fetuses.

Maternal nutrient restriction (NR) causes small for gestational age (SGA) offspring, which are at higher risk for accelerated postnatal growth and developing insulin resistance in adulthood. Skeletal muscle is essential for whole-body glucose metabolism, as 80% of insulin-mediated glucose uptake occurs in this tissue. Maternal NR can alter fetal skeletal muscle mass, expression of glucose transporters, insulin signaling, and myofiber type composition. It also leads to accumulation of intramuscular triglycerides (IMTG), which correlates to insulin resistance. Using a 50% NR treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the NR group. Thus, we classified those fetuses into NR(Non-SGA; n = 11) and NR(SGA; n = 11). The control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and gastrocnemius and soleus muscles were collected. In fetal plasma, total insulin was lower in NR(SGA) fetuses compared NR(Non-SGA) and control fetuses (P < 0.01), whereas total IGF-1 was lower in NR(SGA) fetuses compared with control fetuses (P < 0.05). Within gastrocnemius, protein expression of insulin receptor (INSRB; P < 0.05) and the glucose transporters, solute carrier family 2 member 1 and solute carrier family 2 member 4, was higher (P < 0.05) in NR(SGA) fetuses compared with NR(Non-SGA) fetuses; IGF-1 receptor protein was increased (P < 0.01) in NR(SGA) fetuses compared with control fetuses, and a lower (P < 0.01) proportion of type I myofibers (insulin sensitive and oxidative) was observed in SGA fetuses. For gastrocnemius muscle, the expression of lipoprotein lipase (LPL) messenger RNA (mRNA) was upregulated (P < 0.05) in both NR(SGA) and NR(Non-SGA) fetuses compared with control fetuses, whereas carnitine palmitoyltransferase 1B (CPT1B) mRNA was higher (P < 0.05) in NR(Non-SGA) fetuses compared with control fetuses, but there were no differences (P > 0.05) for protein levels of LPL or CPT1B. Within soleus, there were no differences (P > 0.05) for any characteristic except for the proportion of type I myofibers, which was lower (P < 0.05) in NR(SGA) fetuses compared with control fetuses. Accumulation of IMTG did not differ (P > 0.05) in gastrocnemius or soleus muscles. Collectively, the results indicate molecular differences between SGA and Non-SGA fetuses for most characteristics, suggesting that maternal NR induces a spectral phenotype for the metabolic programming of those fetuses.

Pre-exposure prophylaxis awareness, acceptability and potential stigma among medical and non-medical clinic staff in methadone treatment settings in northern New Jersey: The key role of non-medical staff in enhancing HIV prevention.

BACKGROUND: HIV prevention is needed among people who use drugs (PWUD) due to mixing sex and drugs, selling/trading sex, and/or injecting drugs. Pre-exposure prophylaxis (PrEP) is an extremely effective biomedical HIV prevention strategy, but uptake remains low among communities most in need of HIV prevention, including PWUD. Previous studies have found that providers are less willing to prescribe PrEP to PWUD, yet PWUD express high levels of PrEP acceptance. More research is needed to understand how people who provide substance use treatment services think about PrEP to maximize this biomedical prevention strategy. METHODS: The study conducted semistructured interviews with 29 staff members in two methadone clinic settings in urban northern New Jersey. Staff members included medical providers, methadone counselors, intake coordinators, front desk staff, lab technicians, security guards, and administrative/leadership personnel. RESULTS: All staff recognized the need for HIV prevention among their patient populations, but most were either unaware of PrEP or unfamiliar with its purpose and how it works. Medical providers were more likely to have some PrEP knowledge in comparison to counselors and other staff, but the former largely did not have in-depth knowledge. Among those familiar with PrEP, many confused PrEP with HIV medication, as Truvada was the only FDA-approved PrEP at the time of the study. About half of participants expressed clear support for PrEP, while the other half expressed mixed or negative attitudes related to HIV, sexual behavior, and mistrust of the medication. Both the positive and negative perceptions entailed stigmatizing elements. RECOMMENDATIONS: Due to patients' frequent interactions with non-medical staff (e.g., front desk staff, lab technicians, etc.), all staff, not only medical personnel, should be aware of PrEP and comfortable discussing it to foster well-informed, nonjudgmental conversations about HIV prevention with patients. PrEP education should specifically address HIV and sexual-related stigma, as even positive perceptions of PrEP may entail stigmatizing elements.

Effect of maternal overnutrition on predisposition to insulin resistance in the foal: Foal skeletal muscle development and insulin signaling.

Skeletal muscle plays an integral role in the ability of a horse to perform at high levels. Shifts in skeletal muscle development in response to maternal plane of nutrition may have substantial and lasting impacts on athletic performance and whole-body metabolism. Therefore, sixteen Quarter Horse mares were used in a completely randomized design and maintained at a body condition score (BCS) 6 until start of third trimester. On d 235 of gestation, mares were randomly assigned to receive one of two dietary treatments with a diet formulated to meet requirements during late gestation (CON; n = 8), and an overfed diet (HIGH; n = 8) where mares received an additional 40% above CON. Five h after parturition, foals were euthanized, and gluteus medius, triceps brachii, and semitendinosus were harvested for analyses. Gene expression was determined by qPCR and western immunoblotting was used to quantify total and phosphorylated forms of proteins involved in skeletal muscle metabolism with tubulin as the loading control. All data were analyzed using PROC MIXED of SAS. Foals from HIGH mares exhibited larger skeletal muscle fibers by area (P <0.05), and a shift in muscle fiber development towards type I slow twitch muscle fibers (P <0.05). Relative expression of glucose transporter 4 (GLUT4) was lower in HIGH foals compared to CON in gluteus medius (P = 0.05). Insulin receptor isoform B (INSR-B) and insulin-like growth factor 1 receptor (IGF1R) were greater in triceps brachii of HIGH foals compared to CON (P ≤ 0.03). Insulin receptor isoform A (INSR-A), however, tended to be lower in triceps brachii of HIGH compared to CON (P = 0.10). Ratios of phosphorylated to total extracellular signal-regulated protein kinase 1/2 (ERK1/2) and c-June N-terminal kinase (JNK) were higher in HIGH foals compared to CON (P ≤0.04) in gluteus medius. There were no differences observed for phosphorylated to total protein ratios in semitendinosus and triceps brachii muscles; however, total ERK1/2 tended to be elevated (P <0.10) in semitendinosus from CON foals compared to HIGH. There was no difference in phosphorylated or total protein kinase B (AKT) (P >0.14). These data indicate hypertrophy of skeletal muscle fibers and a shift towards type I slow twitch fibers in HIGH foals. Furthermore, this study identifies muscle specific changes in gene expression and downstream insulin receptor signaling, which may contribute to future metabolic abnormalities in response to maternal overnutrition.

Effect of maternal overnutrition on predisposition to insulin resistance in the foal: Maternal parameters and foal pancreas histoarchitecture.

Results from previous studies indicate that maternal overnutrition during late gestation predisposes foals to metabolic disease, however, specific mechanisms resulting in disease remain unknown. Quarter Horse mares (n = 16), were randomly assigned to dietary treatments, beginning on gestational day 235, and consisted of a control group (CON- diet meeting nutrient requirement; n = 8) or an overfed diet (HIGH; n = 8) where mares received an additional 40 % above CON. On gestational days 285 and 315, an intravenous glucose tolerance test (FSIGTT) was conducted. Following parturition, foals were separated from the mare, prohibited from nursing, and an FSIGTT was conducted at 2 h postpartum. Foals were immediately euthanized and tissues preserved for analyses. There was no effect of treatment on foal BW (P = 0.50), pancreas weight (P = 0.60), or FSIGTT area under the curve for glucose (P = 0.80) and insulin (P = 0.70). Colocalization of α-amylase to isolate pancreatic islets of Langerhans indicated increased islet number and size in foals from HIGH mares (P < 0.01). Immunofluoresent analysis of insulin, glucagon, and somatostatin indicate no difference in intensity of staining (P> 0.10). Foals exposed to overnutrition during peak fetal growth had altered pancreatic islet development that may lead to adult-onset metabolic disease.

Chirping response of weakly electric knife fish (Apteronotus leptorhynchus) to low-frequency electric signals and to heterospecific electric fish.

Brown ghost knife fish (Apteronotus leptorhynchus) can briefly increase their electric organ discharge (EOD) frequency to produce electrocommunication signals termed chirps. The chirp rate increases when fish are presented with conspecific fish or high-frequency (700-1100 Hz) electric signals that mimic conspecific fish. We examined whether A. leptorhynchus also chirps in response to artificial low-frequency electric signals and to heterospecific electric fish whose EOD contains low-frequency components. Fish chirped at rates above background when presented with low-frequency (10-300 Hz) sine-wave stimuli; at 30 and 150 Hz, the threshold amplitude for response was 1 mV cm(-1). Low-frequency (30 Hz) stimuli also potentiated the chirp response to high-frequency ( approximately 900 Hz) stimuli. Fish increased their chirp rate when presented with two heterospecific electric fish, Sternopygus macrurus and Brachyhypopomus gauderio, but did not respond to the presence of the non-electric fish Carassius auratus. Fish chirped to low-frequency (150 Hz) signals that mimic those of S. macrurus and to EOD playbacks of B. gauderio. The response to the B. gauderio playback was reduced when the low-frequency component (<150 Hz) was experimentally filtered out. Thus, A. leptorhynchus appears to chirp specifically to the electric signals of heterospecific electric fish, and the low-frequency components of heterospecific EODs significantly influence chirp rate. These results raise the possibility that chirps function to communicate to conspecifics about the presence of a heterospecific fish or to communicate directly to heterospecific fish.

Effect of maternal nutrient restriction on skeletal muscle mass and associated molecular pathways in SGA and Non-SGA sheep fetuses.

Maternal nutrient restriction causes small for gestational age (SGA) offspring, which exhibit a higher risk for metabolic syndrome in adulthood. Fetal skeletal muscle is particularly sensitive to maternal nutrient restriction, which impairs muscle mass and metabolism. Using a 50% nutrient restriction treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the nutrient-restricted (NR) group. Thus, our objective was to evaluate the effect of maternal NR on muscle mass, myofiber hypertrophy, myonuclear dotation, and molecular markers for protein synthesis and degradation, while accounting for the observed fetal weight variation. Within the NR group, we classified upper-quartile fetuses into NR(Non-SGA) (n = 11) and lower-quartile fetuses into NR(SGA) (n = 11). A control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and organs were collected, and gastrocnemius and soleus muscles were sampled for investigation. Results showed decreased (P < 0.05) absolute tissue/organ weights, including soleus and gastrocnemius muscles, in NR(SGA) fetuses compared to NR(Non-SGA) and control. Myofiber cross-sectional area was smaller in NR(SGA) vs control for gastrocnemius (P = 0.0092) and soleus (P = 0.0097) muscles. Within the gastrocnemius muscle, the number of myonuclei per myofiber was reduced (P = 0.0442) in NR(SGA) compared to control. Cortisol may induce protein degradation. However, there were no differences in fetal cortisol among groups. Nevertheless, for gastrocnemius muscle, cortisol receptor (NR3C1; P = 0.0124), and FOXO1 (P = 0.0131) were upregulated in NR(SGA) compared to control while NR(Non-SGA) did not differ from the other 2 groups. KLF15 was upregulated (P = 0.0002) in both NR(SGA) and NR(Non-SGA); while FBXO32, TRIM63, BCAT2 or MSTN did not differ. For soleus muscle, KLF15 mRNA was upregulated (P = 0.0145) in NR(SGA) compared to control, and expression of MSTN was increased (P = 0.0259) in NR(SGA) and NR(Non-SGA) compared to control. At the protein level, none of the mentioned molecules nor total ubiquitin-labeled proteins differed among groups (P > 0.05). Indicators of protein synthesis (total and phosphorylated MTOR, EI4EBP1, and RPS6KB1) did not differ among groups in either muscle (P > 0.05). Collectively, results highlight that maternal NR unequally affects muscle mass in NR(SGA) and NR(Non-SGA) fetuses, and alterations in myofiber cross-sectional area and myonuclei number partially explain those differences.

"Worn out": Coping strategies for managing antiretroviral treatment fatigue among urban people of color living with HIV who were recently disengaged from outpatient HIV care.

Antiretroviral-related treatment fatigue is inconsistently defined in the literature on barriers to ART adherence. Research suggests that treatment fatigue is a salient challenge for people struggling with antiretroviral therapy adherence, but little is known about how people living with HIV attempt to manage this fatigue. Twenty-seven semi-structured interviews were conducted with low-income people of color living with HIV in NYC that were currently, or recently, disengaged from HIV care. The findings from this exploratory study suggest that treatment fatigue was common and that participants devised personal strategies to overcome it. These strategies included using reminder programs, requesting weekly rather than monthly pill quantities, and taking "pill holidays". The varied nature- and varying levels of effectiveness- of these strategies highlight the need for specific programming to provide tailored support. Future research should examine treatment fatigue as a specific subtype of adherence challenge, and aim to define pill fatigue clearly.

Calcium channels coupled to glutamate release identified by omega-Aga-IVA.

Presynaptic calcium channels are crucial elements of neuronal excitation-secretion coupling. In mammalian brain, they have been difficult to characterize because most presynaptic terminals are too small to probe with electrodes, and available pharmacological tools such as dihydropyridines and omega-conotoxin are largely ineffective. Subsecond measurements of synaptosomal glutamate release have now been used to assess presynaptic calcium channel activity in order to study the action of peptide toxins from the venom of the funnel web spider Agelenopsis aperta, which is known to inhibit dihydropyridine and omega-conotoxin-resistant neuronal calcium currents. A presynaptic calcium channel important in glutamate release is shown to be omega-Aga-IVA sensitive and omega-conotoxin resistant.

Distinct, convergent second messenger pathways modulate neuronal calcium currents.

Norepinephrine (NE) and gamma-aminobutyric acid (GABA) inhibit N-type calcium channels in embryonic chick sensory neurons. We demonstrate here that the modulatory actions of the two transmitters are mediated through distinct biochemical pathways. Intracellular application of the pseudosubstrate inhibitor for protein kinase C blocks the inhibition produced by NE (and the protein kinase C activator oleoylacetylglycerol), but not that produced by GABA. Calcium current inhibition produced by oleoylacetylglycerol occludes inhibition by subsequent application of NE; GABA-mediated inhibition, however, is not eliminated by prior activation of protein kinase C. These results demonstrate that multiple biochemical pathways converge to control N-type calcium channel function.

Two subcellular mechanisms underlie calcium-dependent facilitation of bioluminescence.

Epithelial calcium action potentials in Obelia geniculata trigger brief light flashes from specialized cells by direct activation of cytoplasmic calcium-activated photoprotein obelin. During a series of action potentials, sequential flashes undergo characteristic facilitation and decrement with no change in associated spike waveform. Analysis of the subcellular light distribution shows that facilitation results from two processes: recruitment of calcium entry sites and increased light from previously responding localized sites. We propose a model that accounts for the localized flash facilitation and decrement observed in vivo and is based upon the kinetics of calcium binding and emission of obelin. In this model, obelin emits light only when three calcium ions are bound. Changes in flash intensity during successive action potentials result from calcium bound persistently to unexpended obelin, effectively lowering the number of calcium ions required for subsequent activation. Accordingly, facilitation or decrement results from the time-dependent availability of singly and doubly bound obelin.

Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus.

N-type calcium channels play a dominant role in controlling synaptic transmission in many peripheral neurons. Transmitter release from mammalian central nerve terminals, however, is relatively resistant to the N channel antagonist omega-conotoxin GVIA. We studied the sensitivity of glutamatergic synaptic transmission in rat hippocampal slices to omega-conotoxin and to omega-Aga-IVA, a P channel antagonist. Both toxins reduced the amplitude of excitatory postsynaptic potentials in CA1 pyramidal neurons, but omega-Aga-IVA was the more rapid and efficacious. These results were corroborated by biochemical studies measuring subsecond, calcium-dependent [3H]glutamate release from hippocampal synaptosomes. Thus, at least two calcium channel types trigger glutamate release from hippocampal neurons, but P-type plays a more prominent role. Eliminating synaptic transmission in the CNS, therefore, may require inhibiting more than a single calcium channel type.

Intercellular signaling as visualized by endogenous calcium-dependent bioluminescence.

Bioluminescence in the hydrozoan coelenterate Obelia results from calcium activation of a photoprotein contained in light-emitting cells (photocytes) scattered in the animal's endoderm. The influx of calcium into nonluminescent endodermal cells through conventional voltage-dependent calcium channels is required for the excitation-luminescence coupling. Our results suggest that the subsequent diffusion of this calcium, via gap junctions, into the neighboring photocytes triggers a localized luminescence response. Following intense stimulation, the local rise in calcium elicits a secondary wave of luminescence that is supported by a voltage-independent calcium permeability mechanism in the photocyte plasma membrane. These two mechanisms for elevating internal calcium in light-emitting cells can account for the spatial and temporal features of intracellular luminescence in Obelia.

Transmitter-mediated inhibition of N-type calcium channels in sensory neurons involves multiple GTP-binding proteins and subunits.

The modulation of voltage-activated Ca2+ channels by neurotransmitters and peptides is very likely a primary means of regulating Ca(2+)-dependent physiological functions such as neurosecretion, muscle contraction, and membrane excitability. In neurons, N-type Ca2+ channels (defined as omega-conotoxin GVIA-sensitive) are one prominent target for transmitter-mediated inhibition. This inhibition is widely thought to result from a shift in the voltage independence of channel gating. Recently, however, voltage-independent inhibition has also been described for N channels. As embryonic chick dorsal root ganglion neurons express both of these biophysically distinct modulatory pathways, we have utilized these cells to test the hypothesis that the voltage-dependent and -independent actions of transmitters are mediated by separate biochemical pathways. We have confirmed this hypothesis by demonstrating that the two modulatory mechanisms activated by a single transmitter involve not only different classes of G protein but also different G protein subunits.

Specific inhibitors of protein kinase C block transmitter-induced modulation of sensory neuron calcium current.

Modulation of neuronal, voltage-dependent calcium current has been described for a number of transmitters and peptides, but the biochemical basis for this phenomenon has not been completely identified. In several cases protein kinase C (PKC) is thought to mediate transmitter inhibition of calcium current; however, a lack of specific PKC inhibitors has hampered a direct physiological test of this idea. We have used the whole-cell, tight-seal configuration of the patch-clamp technique to apply intracellularly two specific PKC inhibitors to the cell bodies of embryonic chick sensory neurons. Both inhibitors, a 17 kd protein purified from bovine brain and a synthetic 13 amino acid "pseudosubstrate" peptide, blocked inhibition of calcium current by either norepinephrine or an exogenously applied PKC activator. These results provide strong evidence that activation of PKC is a prerequisite for the modulation of sensory neuron calcium current by norepinephrine.

G protein-coupled receptor kinase mediates desensitization of norepinephrine-induced Ca2+ channel inhibition.

G protein-coupled receptors are essential signaling molecules at sites of synaptic transmission. Here, we explore the mechanisms responsible for the use-dependent termination of metabotropic receptor signaling in embryonic sensory neurons. We report that the inhibition of voltage-dependent Ca2+ channels mediated by alpha2-adrenergic receptors desensitizes slowly with prolonged exposure to the transmitter and that the desensitization is mediated by a G protein-coupled receptor kinase (GRK). Intracellular introduction of recombinant, purified kinases or synthetic blocking peptides into individual neurons demonstrates the specific involvement of a GRK3-like protein. These results suggest that GRK-mediated termination of receptor-G protein coupling is likely to regulate synaptic strength and, as such, may provide one effective mechanism for depression of synaptic transmission.

Altered functional expression of Purkinje cell calcium channels precedes motor dysfunction in tottering mice.

In tottering mice, a point mutation in the gene encoding P-type (Ca(v)2.1) voltage-gated calcium channels results in ataxia, absence epilepsy, and motor dystonia that appear 3-4 weeks postnatally. The aberrant motor behaviors have been linked to cerebellar dysfunction, and adult Purkinje cells (PCs) of tottering mice exhibit calcium-dependent changes in gene transcription suggestive of altered calcium homeostasis. In an attempt to identify early postnatal events important for the development of the behavioral phenotype, we examined calcium channel expression in cerebellar PCs from postnatal days 6-15 (P6-15). Whole cell recording was combined with selective calcium channel antagonists to allow discrimination of the various voltage-activated calcium channels types; early age-dependent differences between tottering and wild-type PCs were found. Wild-type PCs experienced a steady increase in P current density over this period, resulting in a twofold change by P15. In tottering, by contrast, P current density remained unchanged from P6-8 and was only 25% of the wild-type level by P8. A developmental delay in functional expression was implicated in this early deficit, since ensuing gains over the subsequent week brought tottering P current density close to the wild-type level by P15. At this age, tottering PCs also exhibited a 2.2-fold higher L-type calcium current density than that expressed by wild-type PCs. Increases in N current were apparent at some ages, most strikingly within a subset of tottering PCs at P15. Functional R- and T-type calcium current densities were equivalent to wild-type levels at all ages. We conclude that the tottering mutation brings about selective changes in functional calcium channel expression 1 to 2 weeks prior to the appearance of the behavioral deficits, raising the possibility that they represent an early, primary event along the path to motor dysfunction in tottering.

Exocytotic Ca2+ channels in mammalian central neurons.

Intracellular Ca2+ initiates physiological events as diverse as gene transcription, muscle contraction, cell division and exocytosis. Predictably, the metabolic machinery that elicits and responds to changes in intracellular Ca2+ is correspondingly heterogeneous. This review focuses on one element of this complex web that is of particular importance to neurobiologists: identifying which members of the voltage-dependent Ca(2+)-channel superfamily are responsible for the Ca2+ that enters nerve terminals and elicits vesicular release of chemical transmitters.

Ovine endogenous betaretroviruses (enJSRVs) and placental morphogenesis.

Endogenous retroviruses (ERVs) account for a substantial portion of the genetic pool of every animal species (e.g. approximately 8% of the human genome). Despite their overwhelming abundance in nature, many questions on the basic biology of ERVs are unanswered. The most important question derives from the observations in many animal species, including humans, of abundant ERVs expressed in the female genital tract. Sheep harbor approximately 20 copies of endogenous betaretroviruses (enJSRVs), which are related to an exogenous oncogenic virus, Jaagsiekte sheep retrovirus (JSRV). enJSRVs are abundantly expressed in the ovine placenta and uterine endometrium throughout gestation. Hyaluronidase 2 (HYAL2), which can serve as a cellular receptor for JSRV and enJSRVs envelope (Env), is expressed by the trophoblast giant binucleate cells and multinucleated syncytia of the placenta. Little is known about the cellular and molecular mechanisms that regulate trophoblast differentiation and syncytia formation during synepitheliochorial placentation in sheep. The temporal and spatial alterations in enJSRVs expression in the ovine uterus and placenta support the hypothesis that trophoblast growth and differentiation into binucleate cells and formation of multinucleated syncytiotrophoblast involves enJSRVs Env and possibly their cellular receptor, HYAL2.