Can splenocytes enhance pancreatic β-cell function and mass in 90% pancreatectomized rats fed a high fat diet?

AimsRecent studies have shown that splenocytes may act as a possible neogenic source with regard to β-cells in rodent diabetic models. Accordingly, we sought to determine whether splenocytes played an important role in promoting β-cell function and mass among type 2 diabetic rats with and without spleen.Main methodsWe randomly divided female 90% pancreatectomized (Px) Sprague Dawley rats into three groups: splenectomy (SPX), splenectomy plus the injection of male splenocytes (SPI), and no splenectomy (NSP). They were administered with 40 energy percent fat diets over the course of five weeks. At the end of the experimental period, insulin secretion capacity was measured by hyperglycemic clamp. At 6 h after BrdU⁺ injection, the pancreas was prepared with 4% paraformaldehyde in order to perform immunohistochemistry.Key findingsSPX increased and sustained serum glucose levels more than NSP and SPI during oral glucose tolerance testing. During hyperglycemic clamp, first and second phase insulin secretion decreased in the SPX rats while splenocyte injections counteracted this. Beta-cell mass in the SPX group was reduced more than among NSP and SPI. This was the result of a decrease in the number of small β-cell clusters in SPX, which is indicative of a decrease in β-cell neogenesis.SignificanceSplenocytes play an important role with regard to the neogenesis of β-cells in insulin deficient type 2 diabetic rats, although they are not critical for β-cell regeneration.     

The interaction of neurotrophins with the p75NTR common neurotrophin receptor: a comprehensive molecular modeling study

Neurotrophins are a family of proteins with pleiotropic effects mediated by two distinct receptor types, namely the Trk family, and the common neurotrophin receptor p75NTR. Binding of four mammalian neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), to p75NTR is studied by molecular modeling based on X-ray structures of the neurotrophins and the extracellular domain of p55TNFR, a homologue of p75NTR. The model of neurotrophin/receptor interactions suggests that the receptor binding domains of neurotrophins (loops I and IV) are geometrically and electrostatically complementary to a putative binding site of p75NTR, formed by the second and part of the third cysteine-rich domains. Geometric match of neurotrophin/receptor binding domains in the complexes, as characterized by shape complementarity statistic Sc, is comparable to known protein/protein complexes. All charged residues within the loops I and IV of the neurotrophins, previously determined as being critical for p75NTR binding, directly participate in receptor binding in the framework of the model. Principal residues of the binding site of p75NTR include Asp47, Lys56, Asp75, Asp76, Asp88, and Glu89. The additional involvement of Arg80 and Glu53 is specific for NGF and BDNF, respectively, and Glu73 participates in binding with NT-3 and NT-4/5. Neurotrophins are likely to induce similar, but not identical, conformational changes within the p75NTR binding site.     

Genbank accession #: AJ131961

Plant Molecular Biology -     

Injection drug use and HIV/AIDS transmission in China

INTRODUCTION Although sexual transmission accounts for most of the AIDS epidemic globally, HIV/AIDS among injecting drug users (IDUs) is a growing problem worldwide. First de- tected in China in 1989 among drug abusers on the Yunnan border, HIV/AIDS subse…     

Protandrous migration and variation in morphological characters in Emberiza buntings at an East Asian stopover site

The effect of the timing of spring migration on reproductive success differs between the sexes. As a consequence, various sex‐specific tactics relating to the timing of migration have evolved in migratory avian groups. Various hypotheses have been proposed to explain differential migration to breeding or wintering grounds, and inter‐ and intrasexual size differences are often considered one of the proximate mechanisms. We investigated arrival patterns in the spring by individuals of each sex, sexual size dimorphism and related morphological variables, and the relationship between size variation and arrival date in five bunting species that passed through an East Asian migratory flyway stopover site in 2006–08. Males of all the study species arrived before females, and significant sexual dimorphism was observed. Several morphological characters, including total length, wing‐length and tail‐length, contributed to the size variation. Although larger males arrived earlier, there was no relationship between arrival date and size in females. Our study confirmed that East Asian buntings display a discriminated protandrous migration pattern at the stopover site as well as at the breeding grounds. This is consistent with the view that larger body size in males is favoured due to its association with early arrival to help ensure access to the best resources and hence enhanced mating success.     

Transmission potential,skin inflammatory response,and parasitism of symptomatic and asymptomatic dogs with visceral leishmaniasis

Background

Visceral leishmaniasis in Brazil is caused by the protozoan Leishmania (Leishmania) chagasi and it is transmitted by sandfly of the genus Lutzomyia. Dogs are an important domestic reservoir, and control of the transmission of visceral leishmaniasis (VL) to humans includes the elimination of infected dogs. However, though dogs are considered to be an important element in the transmission cycle of Leishmania, the identification of infected dogs representing an immediate risk for transmission has not been properly evaluated. Since it is not possible to treat infected dogs, they are sacrificed when a diagnosis of VL is established, a measure that is difficult to accomplish in highly endemic areas. In such areas, parameters that allow for easy identification of reservoirs that represents an immediate risk for transmission is of great importance for the control of VL transmission. In this study we aimed to identify clinical parameters, reinforced by pathological parameters that characterize dogs with potential to transmit the parasite to the vector.

Results

The major clinical manifestations of visceral leishmaniasis in dogs from an endemic area were onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. The transmission potential of these dogs was assessed by xenodiagnosis using Lutzomyia longipalpis. Six of nine symptomatic dogs were infective to Lutzomyia longipalpis while none of the five asymptomatic dogs were infective to the sandfly. Leishmania amastigotes were present in the skin of all clinically symptomatic dogs, but absent in asymptomatic dogs. Higher parasite loads were observed in the ear and ungueal region, and lower in abdomen. The inflammatory infiltrate was more intense in the ears and ungueal regions of both symptomatic and asymptomatic dogs. In clinically affected dogs in which few or none Leishmania amastigotes were observed, the inflammatory infiltrate was constituted mainly of lymphocytes and macrophages. When many parasites were present, the infiltrate was also comprised of lymphocytes and macrophages, as well as a larger quantity of polymorphonuclear neutrophils (PMNs).

Conclusion

Dogs that represent an immediate risk for transmission of Leishmania in endemic areas present clinical manifestations that include onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. Lymphadenopathy in particular was a positive clinical hallmark since it was closely related to the positive xenodiagnosis.

     

The binding of zinc and copper ions to nerve growth factor is differentially affected by pH: implications for cerebral acidosis

It has recently been shown that transition metal cations Zn2+ and Cu2+ bind to histidine residues of nerve growth factor (NGF) and other neurotrophins (a family of proteins important for neuronal survival) leading to their inactivation. Experimental data and theoretical considerations indicate that transition metal cations may destabilize the ionic form of histidine residues within proteins, thereby decreasing their pK(a) values. Because the release of transition metal cations and acidification of the local environment represent important events associated with brain injury, the ability of Zn2+ and Cu2+ to bind to neurotrophins in acidic conditions may alter neuronal death following stroke or as a result of traumatic injury. To test the hypothesis that metal ion binding to neurotrophins is influenced by pH, the effects of Zn2+ and Cu2+ on NGF conformation, receptor binding and NGF tyrosine kinase (trkA) receptor signal transduction were examined under conditions mimicking cerebral acidosis (pH range 5.5-7.4). The inhibitory effect of Zn2+ on biological activities of NGF is lost under acidic conditions. Conversely, the binding of Cu2+ to NGF is relatively independent of pH changes within the studied range. These data demonstrate that Cu2+ has greater binding affinity to NGF than Zn2+ at reduced pH, consistent with the higher affinity of Cu2+ for histidine residues. These findings suggest that cerebral acidosis associated with stroke or traumatic brain injury could neutralize the Zn2+-mediated inactivation of NGF, whereas corresponding pH changes would have little or no influence on the inhibitory effects of Cu2+. The importance of His84 of NGF for transition metal cation binding is demonstrated, confirming the involvement of this residue in metal ion coordination.