Açık barınaklarda yetiştirilen simmental i̇neklerinde soğuk stresinin süt verimi, süt bileşimi ve bazı davranış özelliklerine etkisi

The aim of this study was to determine effect of cold stress on milk yield, milk composition and some behavioural patterns of Simmental dairy cattle kept in open shed barns. In the present study, daily milk yield, milk content, somatic cell count (SCC) in milk and some behavioural patterns of Simmental dairy cattle during winter were determined. Besides, wind chill temperature (WCT) was calculated by using wind speed, temperature and relative humidity rate. In the present study, diffence between mean value of wind speed, temperature, relative humidity rate and WCT characteristics were proved as significant (P<0.01) depending on months in winter. Difference between mean value determined in months winter as for milk composition traits such as protein and total dry matter rate, and SCC were proved as significant (P<0.05). It was also confirmed that negative phenotypic correlation exists between milk fat and total dry matter rate, and WCT (P<0.05). There were also significant differences as for rate of incidence of behavioural patterns such as lying and walking during months winter (P<0.05). In conclusion, it was determined that cold stress affects protein and total dry matter rate in milk, SCC and behavior patterns such as lying and walking of Simmental dairy cattle.Bu araştırma, Simmental ineklerde soğuk stresinin süt verimi, süt bileşimi ve bazı davranış özelliklerine etkisini belirlemek amacıyla yapılmıştır. Araştırmada, Simmental ineklerin kış mevsimindeki günlük süt verimi, sütün bileşimi, sütteki somatik hücre sayısı (SHS) ve bazı davranış özellikleri belirlenmiştir. Ayrıca, rüzgar hızı, çevre sıcaklığı ve bağıl nem oranı tespit edilerek rüzgar soğutma indeksi (RSİ) hesaplanmıştır. Araştırmada, kış mevsimindeki aylara göre rüzgar hızı, çevre sıcaklığı, bağıl nem oranı ve RSİ özelliklerinin ortalama değerleri arasındaki fark önemli (P<0,01) olarak belirlenmiştir. Süt bileşimi özelliklerinden protein ve toplam kuru madde oranları ile SHS’nın kış aylarında belirlenen ortalama değerleri arasındaki farkın önemli (P<0,05) olduğu belirlenmiştir. Ayrıca, süt yağ ve toplam kuru madde oranının RSİ ile arasında negatif fenotipik korrelasyon olduğu saptanmıştır (P<0,05). Davranış özelliklerinden yatma ve yürüme davranışlarının kış aylarındaki oranlarının önemli düzeyde farklılık gösterdiği belirlenmiştir (P<0,05). Sonuç olarak, açık barınakta yetiştirilen Simmental ineklerde soğuk stresinin sütteki protein ve toplam kuru madde oranı ile SHS değerlerini ve yatma ve yürüme davranışlarını etkilediği belirlenmiştir

Evaluation of bcl-2, bax and c-erbB-2 Levels in Chronic Otitis Patients with or without Cholesteatoma

Objective:The aim of this study was to evaluate bcl-2, bax, and c-erbB-2 expressions in primary and secondary acquired cholesteatoma and to indicate the role of apoptosis and accompanying increased cellular proliferation in the pathogenesis of cholesteatoma.Methods:Samples obtained from the skin of the external ear canal (EEC) of patients operated for chronic otitis media (COM) without cholesteatoma constituted Group 1; samples from the EEC skin of patients in Group 3 operated for COM with cholesteatoma and from the EEC skin of patients in Group 4 constituted Group 2; samples obtained from the cholesteatoma matrix of patients operated for COM with primary acquired cholesteatoma constituted Group 3; and samples obtained from the cholesteatoma matrix of patients operated for COM with secondary acquired cholesteatoma constituted Group 4. The assessment of the positive cell ratio was based on the presence of the following findings and was semiquantitatively classified into four groups: 0, no staining; + cell staining (weak positive staining: 1%–33%); ++ cell staining (moderately positive staining: 34%–66%); and +++ cell staining (strong positive staining: 67%–100%).Results:Comparison of the staining scores of bcl-2, bax, and c-erbB-2 revealed a statistically insignificant difference in the staining of samples obtained from the EEC skin (p>0.05). Decreased bcl-2 expression and increased bax and c-erbB-2 expressions were determined in primary and secondary acquired cholesteatoma epithelium compared with the EEC skin of patients operated for COM with or without cholesteatoma, and the differences were found to be statistically significant (p<0.05).Conclusion:In acquired cholesteatoma epithelium, the finding of decreased bcl-2 expression as well as increased bax and c-erbB-2 expressions compared with the EEC skin is an indicator of the increase in both cellular proliferation and apoptosis

De novo variants of CSNK2B cause a new intellectual disability-craniodigital syndrome by disrupting the canonical Wnt signaling pathway

CSNK2B encodes for casein kinase II subunit beta (CK2b), the regulatory subunit of casein kinase II (CK2), which is known to mediate diverse cellular pathways. Variants in this gene have been recently identified as a cause of Poirier-Bienvenu neurodevelopmental syndrome (POBINDS), but functional evidence is sparse. Here, we report five unrelated individuals: two of them manifesting POBINDS, while three are identified to segregate a new intellectual disability-craniodigital syndrome (IDCS), distinct from POBINDS. The three IDCS individuals carried two different de novo missense variants affecting the same codon of CSNK2B. Both variants, NP_001311.3; p.Asp32His and NP_001311.3; p.Asp32Asn, lead to an upregulation of CSNK2B expression at transcript and protein level, along with global dysregulation of canonical Wnt signaling. We found impaired interaction of the two key players DVL3 and b-catenin with mutated CK2b. The variants compromise the kinase activity of CK2 as evident by a marked reduction of phosphorylated b-catenin and consequent absence of active b-catenin inside nuclei of the patient-derived lymphoblastoid cell lines (LCLs). In line with these findings, whole-transcriptome profiling of patient-derived LCLs harboring the NP_001311.3; p.Asp32His variant confirmed a marked difference in expression of genes involved in the Wnt signaling pathway. In addition, whole-phosphoproteome analysis of the LCLs of the same subject showed absence of phosphorylation for 313 putative CK2 substrates, enriched in the regulation of nuclear b-catenin and transcription of the target genes. Our findings suggest that discrete variants in CSNK2B cause dominant-negative perturbation of the canonical Wnt signaling pathway, leading to a new craniodigital syndrome distinguishable from POBINDS

Endometriose cutânea Cutaneous endometriosis

A endometriose é definida como a presença de glândulas endometriais e estroma fora da cavidade uterina. Essa doença, comum nas mulheres, é geralmente observada durante os anos reprodutivos. Embora a pelve seja o sítio mais comum da endometriose em mulheres, a localização extrapélvica é menos frequente e ainda mais difícil de diagnosticar, em decorrência das apresentações distintas. Neste artigo é descrito um caso de endometriose de cicatriz da parede abdominal.Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity. This disease is commonly observed in women, particularly those of reproductive age. The pelvis is the most common location for endometriosis. On the other hand, extrapelvic endometriosis, which is less common, is more difficult to diagnose because of the extreme differences in its presentation. In this article, we describe our experience of a case of endometriosis in an abdominal wall scar

Antimicrobial cerium ion-chitosan crosslinked alginate biopolymer films: A novel and potential wound dressing

Wound dressings require good antiseptic properties, mechanical strength and, more trustably, natural material ingredients. Antimicrobial properties of cerium ions and chitosan are known and alginate based wound dressings are commercially available. In this study, the advantages of these materials were combined and alginate films were crosslinked with cerium(III) solution and chitosan added cerium(III) solution. Films were characterized by Fourier transform infrared spectroscopy (FTIR), light transmittance, scanning electron microscopy (SEM), swelling expefiments, water vapor transmittance tests, and mechanical stretching tests. The antibacterial and physical properties of the films were compared with those of conventional calcium alginate films. Both cerium ion crosslinked and cerium ion-chitosan crosslinked alginate films gained antibacterial activity against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Cerium alginate-chitosan films showed high resistance to being deformed elastically. Results show that cerium alginate-chitosan films can be flexible, ultraviolet protecting, and antibacterial wound dressings. (C) 2017 Elsevier B.V. All rights reserved

Loss-of-function variants in DNM1 cause a specific form of developmental and epileptic encephalopathy only in biallelic state

Background Developmental and epileptic encephalopathies (DEEs) represent a group of severe neurological disorders characterised by an onset of refractory seizures during infancy or early childhood accompanied by psychomotor developmental delay or regression. DEEs are genetically heterogeneous with, to date, more than 80 different genetic subtypes including DEE31 caused by heterozygous missense variants in DNM1. Methods We performed a detailed clinical characterisation of two unrelated patients with DEE and used whole-exome sequencing to identify causative variants in these individuals. The identified variants were tested for cosegregation in the respective families. Results We excluded pathogenic variants in known, DEE-associated genes. We identified homozygous nonsense variants, c.97C>T; p.(Gln33*) in family 1 and c.850C>T; p.(Gln284*) in family 2, in the DNM1 gene, indicating that biallelic, loss-of-function pathogenic variants in DNM1 cause DEE. Conclusion Our finding that homozygous, loss-of-function variants in DNM1 cause DEE expands the spectrum of pathogenic variants in DNM1. All parents who were heterozygous carriers of the identified loss-of-function variants were healthy and did not show any clinical symptoms, indicating that the type of mutation in DNM1 determines the pattern of inheritance

Modifier Genes in Microcephaly: A Report on WDR62, CEP63, RAD50 and PCNT Variants Exacerbating Disease Caused by Biallelic Mutations of ASPM and CENPJ

Congenital microcephaly is the clinical presentation of significantly reduced head circumference at birth. It manifests as both non-syndromic-microcephaly primary hereditary (MCPH)-and syndromic forms and shows considerable inter- and intrafamilial variability. It has been hypothesized that additional genetic variants may be responsible for this variability, but data are sparse. We have conducted deep phenotyping and genotyping of five Pakistani multiplex families with either MCPH (n = 3) or Seckel syndrome (n = 2). In addition to homozygous causal variants in ASPM or CENPJ, we discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT-genes already known to be associated with neurological disorders. MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features. Likewise, the phenotype of Seckel syndrome caused by a novel CENPJ variant was aggravated to microcephalic osteodysplastic primordial dwarfism type II (MOPDII) in conjunction with an additional PCNT variant. We show that the CENPJ missense variant impairs splicing and decreases protein expression. We also observed centrosome amplification errors in patient cells, which were twofold higher in MOPDII as compared to Seckel cells. Taken together, these observations advocate for consideration of additional variants in related genes for their role in modifying the expressivity of the phenotype and need to be considered in genetic counseling and risk assessment

Mutations in CKAP2L, the human homolog of the mouse Radmis gene, cause Filippi syndrome.

Filippi syndrome is a rare, presumably autosomal-recessive disorder characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features, including a broad nasal bridge and underdeveloped alae nasi. Some affected individuals have intellectual disability, seizures, undescended testicles in males, and teeth and hair abnormalities. We performed homozygosity mapping and whole-exome sequencing in a Sardinian family with two affected children and identified a homozygous frameshift mutation, c.571dupA (p.Ile191Asnfs∗6), in CKAP2L, encoding the protein cytoskeleton-associated protein 2-like (CKAP2L). The function of this protein was unknown until it was rediscovered in mice as Radmis (radial fiber and mitotic spindle) and shown to play a pivotal role in cell division of neural progenitors. Sanger sequencing of CKAP2L in a further eight unrelated individuals with clinical features consistent with Filippi syndrome revealed biallelic mutations in four subjects. In contrast to wild-type lymphoblastoid cell lines (LCLs), dividing LCLs established from the individuals homozygous for the c.571dupA mutation did not show CKAP2L at the spindle poles. Furthermore, in cells from the affected individuals, we observed an increase in the number of disorganized spindle microtubules owing to multipolar configurations and defects in chromosome segregation. The observed cellular phenotypes are in keeping with data from in vitro and in vivo knockdown studies performed in human cells and mice, respectively. Our findings show that loss-of-function mutations in CKAP2L are a major cause of Filippi syndrome

An update of pathogenic variants in ASPM, WDR62, CDK5RAP2, STIL, CENPJ, and CEP135 underlying autosomal recessive primary microcephaly in 32 consanguineous families from Pakistan

Background: Primary microcephaly (MCPH) is a congenital neurodevelopmental disorder manifesting as small brain and intellectual disability. It underlies isolated reduction of the cerebral cortex that is reminiscent of early hominids which makes it suitable model disease to study the hominin-specific volumetric expansion of brain. Mutations in 25 genes have been reported to cause this disorder. Although majority of these genes were discovered in the Pakistani population, still a significant proportion of these families remains uninvestigated. Methods: We studied a cohort of 32 MCPH families from different regions of Pakistan. For disease gene identification, genome-wide linkage analysis, Sanger sequencing, gene panel, and whole-exome sequencing were performed. Results: By employing these techniques individually or in combination, we were able to discern relevant disease-causing DNA variants. Collectively, 15 novel mutations were observed in five different MCPH genes; ASPM (10), WDR62 (1), CDK5RAP2 (1), STIL (2), and CEP135 (1). In addition, 16 known mutations were also verified. We reviewed the literature and documented the published mutations in six MCPH genes. Intriguingly, our cohort also revealed a recurrent mutation, c.7782_7783delGA;p.(Lys2595Serfs*6), of ASPM reported worldwide. Drawing from this collective data, we propose two founder mutations, ASPM:c.9557C>G;p. (Ser3186*) and CENPJ:c.18delC;p.(Ser7Profs*2), in the Pakistani population. Conclusions: We discovered novel DNA variants, impairing the function of genes indispensable to build a proper functioning brain. Our study expands the mutational spectra of known MCPH genes and also provides supporting evidence to the pathogenicity of previously reported mutations. These novel DNA variants will be helpful for the clinicians and geneticists for establishing reliable diagnostic strategies for MCPH families