Sarcocystis and Its Complications in Camels (Camelus dromedarius) of Eastern Provinces of Iran

The prevalence of Sarcocystis spp. was investigated by gross and histopathological examinations in 250 camels (Camelus dromedarius) slaughtered from 2002 to 2005 in the Mashhad Slaughterhouse, eastern Iran. Samples were taken from the diaphragm, heart, tongue, esophagus and masseter muscles for histopathological studies. No macroscopic sarcocysts were found in the samples at gross inspection. Sarcocysts were detected in 209 of 250 (83.6%) examined camels at histopathological level. The infection rate of the esophagus, heart, masseter muscles, diaphragm, and tongue was 58.8%, 48.0%, 46.8%, 41.6%, and 28.0%, respectively. There was no significant difference in the rate of infection between male (85.8%) and female (81.0%) camels. The tissue response to vital cysts was minimal; however, reaction to the degenerating cysts was severe and caused tissue damages resulting in hyperemia, hemorrhages, mononuclear cell infiltration, necrotic changes, and fibrosis. The wild and domestic carnivores especially dogs may be the final hosts of Sarcocystis spp. in this area.     

Poly(ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination

Cells with non-functional poly(ADP-ribose) polymerase (PARP-1) show increased levels of sister chromatid exchange, suggesting a hyper recombination phenotype in these cells. To further investigate the involvement of PARP-1 in homologous recombination (HR) we investigated how PARP-1 affects nuclear HR sites (Rad51 foci) and HR repair of an endonuclease-induced DNA double-strand break (DSB). Several proteins involved in HR localise to Rad51 foci and HR-deficient cells fail to form Rad51 foci in response to DNA damage. Here, we show that PARP-1 mainly does not localise to Rad51 foci and that Rad51 foci form in PARP-1^–/– cells, also in response to hydroxyurea. Furthermore, we show that homology directed repair following induction of a site-specific DSB is normal in PARP-1-inhibited cells. In contrast, inhibition or loss of PARP-1 increases spontaneous Rad51 foci formation, confirming a hyper recombination phenotype in these cells. Our data suggest that PARP-1 controls DNA damage recognised by HR and that it is not involved in executing HR as such.     

Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study

BackgroundAutism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS) elements in cognition and behavior besides the interaction of angiotensin II (Ang II), the main product of angiotensin-converting enzyme (ACE), with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism.MethodsConsidering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291) with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR) and PCR–restriction fragment length polymorphism (PCR–RFLP) methods.ResultsThere were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64–5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37–3.48 respectively). Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26–2.67). Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008).ConclusionOur data suggests the involvement of RAS genetic diversity in increasing the risk of autism.     

Avian ichnia and other vertebrate trace fossils from the Neogene Red Beds of Tarom valley in north-western Iran

The Neogene Red Beds of the Tarom valley (north-western Iran) include conglomerate, sandstone, marl and gypsum. Avian and mammal footprints were discovered in one of the sandstone layers at the base of a third Miocene stratigraphical unit in the Gilankesheh area located in the east Tarom valley. The avian ichnia include Aviadactyla vialovi, Avipeda filiportatis, Charadriipeda disjuncta, Charadriipeda isp. A and B and cf. Ornithotarnocia lambrechti. Bird feeding traces are preserved as bilobate, loop-shaped, sinusoidal and ring-like traces. We have also identified a reticulate texture of sole scale imprints in some of the avian ichnia. Two mammal footprints of camelid-like artiodactyls are also present with the avian ichno-assemblage.     

Development and validation of a stability-indicating high performance liquid chromatographic (HPLC) assay for biperiden in bulk form and pharmaceutical dosage forms

Current compendial (USP) methods of assay for the analysis of biperiden in bulk form and pharmaceutical dosage forms involve the use of titrimetric and spectrophotometric procedures, respectively. These are non-selective and non-stability-indicating techniques. In this work, a stability-indicating high performance liquid chromatographic assay procedure has been developed and validated for biperiden. The liquid chromatographic separation was achieved isocratically on a symmetry C8 column (150 mm x 3.9 mm i.d., 5 microm particle size) using a mobile phase containing methanol-buffer (50:50, v/v, pH 2.50) at a flow rate of 1 ml/min and UV detection at 205 nm. The buffer was composed of sodium dihydrogen phosphate (50 mM) and 1-heptanesulfonic acid sodium salt (5 mM). The method was linear over the concentration range of 0.5-25 microg/ml (r=0.9998) with a limit of detection and quantitation 0.03 and 0.1 microg/ml, respectively. The method has the requisite accuracy, selectivity, sensitivity and precision to assay biperiden in bulk form and pharmaceutical dosage forms. Degradation products resulting from the stress studies did not interfere with the detection of biperiden and the assay is thus stability-indicating.     

Eocene Bird and Mammal Tracks from the Karaj Formation,Tarom Mountains,Northwestern Iran

A long continuous trackway of a shorebird (cf. Charadriipeda) and a suite of possible Pantodonta (?Corophydon) or Dinocerata tracks are reported from the Eocene Karaj Formation. Fossil footprints are still rare in Iran, described only from two Jurassic and three Tertiary sites. Thus the current record, the third in the Teritary, adds to a sparse record and increases the diversity of known track types.     

Effect of zinc binding on β-amyloid structure and dynamics: implications for Aβ aggregation

Assembly of β-amyloid (Aβ) peptide into toxic oligomers is widely believed to initiate Alzheimer's disease pathogenesis. Under in vitro physiological conditions, zinc (Zn(II)) can bind to Aβ and redirect its assembly from amyloid fibrillar toward less toxic amorphous aggregation. Propensity of Aβ to go toward a specific form of aggregate state is determined by structural and dynamical properties of the initial monomeric as well as the aggregate state. Here we probe the structural and dynamical impact of binding of Zn(II) to monomeric Aβ40 using NMR spectroscopy. To obtain further support for the importance of intrinsic dynamics in the aggregation precursor, ¹⁵N relaxation measurements were also performed for Aβ42, the more fibrillar aggregation-prone variant of Aβ. The combined data suggest that, upon Zn(II)-binding to the N-terminus of Aβ40, a relatively rigid turnlike structure is induced at residues Val²⁴-Lys²⁸ whereas the residues flanking this region become more mobile on the picosecond-to-nanosecond timescale. This is in contrast to the increased rigidity of Aβ42 at the C-terminus, and proposed to be linked to the higher propensity of Zn(II)-bound peptide to form amorphous aggregates with less entropic penalties than their fibrillar counterparts.     

Extracellular phosphorylation of the amyloid β-peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia and associated with progressive deposition of amyloid β-peptides (Aβ) in the brain. Aβ derives by sequential proteolytic processing of the amyloid precursor protein by β- and γ-secretases. Rare mutations that lead to amino-acid substitutions within or close to the Aβ domain promote the formation of neurotoxic Aβ assemblies and can cause early-onset AD. However, mechanisms that increase the aggregation of wild-type Aβ and cause the much more common sporadic forms of AD are largely unknown. Here, we show that extracellular Aβ undergoes phosphorylation by protein kinases at the cell surface and in cerebrospinal fluid of the human brain. Phosphorylation of serine residue 8 promotes formation of oligomeric Aβ assemblies that represent nuclei for fibrillization. Phosphorylated Aβ was detected in the brains of transgenic mice and human AD brains and showed increased toxicity in Drosophila models as compared with non-phosphorylated Aβ. Phosphorylation of Aβ could represent an important molecular mechanism in the pathogenesis of the most common sporadic form of AD.     

Identification of a SLC19A2 nonsense mutation in Persian families with thiamine-responsive megaloblastic anemia

Thiamine-responsive megaloblastic anemia (TRMA) is an autosomal recessive syndrome characterized by early-onset anemia, diabetes, and hearing loss caused by mutations in the SLC19A2 gene. We studied the genetic cause and clinical features of this condition in patients from the Persian population. A clinical and molecular investigation was performed in four patients from three families and their healthy family members. All had the typical diagnostic criteria. The onset of hearing loss in three patients was at birth and one patient also had a stroke and seizure disorder. Thiamine treatment effectively corrected the anemia in all of our patients but did not prevent hearing loss. Diabetes was improved in one patient who presented at the age of 8 months with anemia and diabetes after 2 months of starting thiamine. The coding regions of SLC19A2 were sequenced in all patients. The identified mutation was tested in all members of the families. Molecular analyses identified a homozygous nonsense mutation c.697C > T (p.Gln233*) as the cause of the disease in all families. This mutation was previously reported in a Turkish patient with TRMA and is likely to be a founder mutation in the Persian population.     

Effect of polyamines on the structure, thermal stability and 2,2,2-trifluoroethanol-induced aggregation of alpha-chymotrypsin

Naturally occurring polyamines are known to interact with a variety of biomolecules and critically involve in some important physiological processes. They have also been shown to influence protein aggregation in vitro in some cases. The aim of the present study was to investigate how polyamines may influence the structure and thermal stability of alpha-chymotrypsin and modulate alcohol-induced aggregation of this protein. Various techniques, including turbidity measurements, tensiometry, DSC, intrinsic fluorescence and far- and near-UV circular dichroism spectroscopy were used to examine the effect of putrescine and spermidine on alpha-chymotrypsin. While slight changes in the secondary and tertiary structure of the protein was observed, a clear stabilizing effect against its thermal unfolding was achieved. Moreover, the polyamines were found to inhibit TFE-induced aggregation at 32% TFE and promote formation of non-native alpha-helices in the protein structure. Based on the observed increase in surface tension induced by polyamines, it is suggested that their effects on enhancing thermal stability and alcohol-induced alpha-helices formation may be due to their kosmotropic properties.