Assessment of HER1 (rs11543848) and HER2 (rs1136201) polymorphism and their association with colorectal cancer susceptibility in Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Colorectal cancer (CRC) is a widespread malignancy characterized by uncontrolled growth in the colon or rectum and remains a leading cause of cancer-related mortality globally. Various genes polymorphisms have been linked with the risk of CRC, but our study aimed to investigate the association between HER1 (rs11543848) and HER2 (rs1136201) polymorphisms with the risk of CRC in the Khyber Pakhtunkhwa (KPK) population of Pakistan. The association of the selected polymorphisms (rs11543848 and rs1136201) with CRC risk has been investigated in various ethnic groups, but their impact remains unexplored in Pakistan, particularly within the KPK population, highlighting the need of the study in this region. METHODS: In this study 120 CRC patients and 120 healthy controls were enrolled. The DNA was extracted from the blood by salting-out method and genotyping was done using ARMS-PCR. RESULTS: Our investigations provided convincing evidence of a strong association between HER1 (rs11543848) and the risk of CRC. Both the genotypes heterozygous GA (OR = 2.07, CI = 1.18 to 3.64, P = 0.01) and homozygous AA (OR = 6.22, CI = 2.56 to 15.08, P = 0.0001) showed higher risk and significant association with the CRC risk. Similarly, heterozygous genotype AG of HER2 (rs1136201) was significantly associated (OR = 3.16, 95% CI = 1.78 to 5.58, P = 0.0001) while mutant genotype GG showed higher risk but non-significant association (OR = 3.23, 95% CI = 0.84 to 12.43, P = 0.08) with CRC patients. HER1 (rs11543848) demonstrated a significant association (P = 0.003) with the age at diagnosis in CRC patients, while HER2 (rs1136201) showed a non-significant association (P = 0.434). Both the SNPs were non-significantly associated with gender (P = 0.793 and 0.117), metastasis (P = 0.582 and 0.129), location of the tumor (P = 0.555 and 0.993), tumor grade (P = 0.290 and 0.920), tumor size (P = 0.535 and 0.289) and stages of cancer (P = 0.892 and 0.352). CONCLUSION: In conclusion, both the polymorphisms rs11543848 and rs1136201 displayed susceptibility with CRC in the KPK population. However, further investigations are recommended while using whole exome sequencing on a larger sample size for more precise results.

Multi-stakeholder perspective to generate evidence and strategies for sustainable management of ropes from the fishing sector of Norway.

Marine plastic pollution is a growing stressor affecting both marine and terrestrial life. Plastic polymers are widespread in oceans, including sparsely populated Nordic countries. Norway, a fishing-dominant region, faces substantial plastic pollution from fishing ropes, which often end up incinerated, landfilled, or lost in the ocean, contributing to the ghost fishing problem. This research employs a static material flow analysis (MFA) to assess plastic mass flows and the recyclability of 15 rope types used in Norway's commercial fishing sector. Findings reveal that approximately 383 tons of ropes are lost annually in Norwegian waters, endangering fish species. Furthermore, only one-third of the rope types can be efficiently recycled using available recycling technologies, highlighting the need for circularity. The MFA and inventory-based ranking approach shows significant potential as a holistic decision support tool for industry and policymakers in exercising sustainable and circular management for ropes.

Dominance of Asia II 1 species of Bemisia tabaci in Pakistan and beyond.

Globally, Whitefly (Bemisia tabaci) is one of the most important insect pests of crops that causes huge economical losses. The current study was designed to exclusively screen the B. tabaci species in the cotton field of Pakistan during 2017-2020 and have to conduct comparative analysis of B. tabaci species in Asia where Asia II 1 has been reported. A total of 5142 B. tabaci sequences of mitochondrial cytochrome oxidase 1 (mtCO1) from Asian countries were analyzed to determine the species and their distribution in the region. Our analysis over time and space showed that Asia II 1 has gradually dominated over Asia 1 in Punjab Province and over both Asia 1 and MEAM1 in Sindh Province. Asia has been divided into three regions i.e., South Asia (2524 sequences), Southeast Asia (757 sequences) and East Asia (1569 sequences) and dominance of different species of B. tabaci has been determined by calculating the relative percentage of each species. Interestingly, Asia II 1 has been found dominant in the neighboring region (northern zone) of India and also being dominant in its central zone. The dominance of Asia II 1 in Pakistan and northern India explains whitefly epidemic being reported in recent years.

SARS-CoV-2 variants of concern dominate in Lahore, Pakistan in April 2021.

The SARS-CoV-2 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Indian sub-continent. Pakistan has one of the world's largest populations, of over 200 million people and is experiencing a severe third wave of infections caused by SARS-CoV-2 that began in March 2021. In Pakistan, during the third wave until now only 12 SARS-CoV-2 genomes have been collected and among these nine are from Islamabad. This highlights the need for more genome sequencing to allow surveillance of variants in circulation. In fact, more genomes are available among travellers with a travel history from Pakistan, than from within the country itself. We thus aimed to provide a snapshot assessment of circulating lineages in Lahore and surrounding areas with a combined population of 11.1 million. Within a week of April 2021, 102 samples were sequenced. The samples were randomly collected from two hospitals with a diagnostic PCR cutoff value of less than 25 cycles. Analysis of the lineages shows that the Alpha variant of concern (first identified in the UK) dominates, accounting for 97.9 % (97/99) of cases, with the Beta variant of concern (first identified in South Africa) accounting for 2.0 % (2/99) of cases. No other lineages were observed. In depth analysis of the Alpha lineages indicated multiple separate introductions and subsequent establishment within the region. Eight samples were identical to genomes observed in Europe (seven UK, one Switzerland), indicating recent transmission. Genomes of other samples show evidence that these have evolved, indicating sustained transmission over a period of time either within Pakistan or other countries with low-density genome sequencing. Vaccines remain effective against Alpha, however, the low level of Beta against which some vaccines are less effective demonstrates the requirement for continued prospective genomic surveillance.

Comparative study of the genetic basis of nitrogen use efficiency in wild and cultivated barley.

To curb the increasing demand for nitrogenous fertilizers, it is imperative to develop new cultivars with comparatively greater nitrogen use efficiency (NUE). Nonetheless, so far very meager information is available concerning the variances among barley (Hordeum vulgare L.) varieties for their response to nitrogen deprivation. The current study was carried out to explore the potential of barley genotypes for higher NUE. A hydroponic experiment was conducted at seedling stage to compare the performance of four barley genotypes, ZD9 and XZ149 (with higher NUE) and HXRL and XZ56 (with lower NUE) in response to low (0.1 mM) and normal nitrogen (2 mM) levels. Under low N, all the genotypes expressed less number of tillers, decreased soluble proteins, chlorophyll and N concentrations in both roots and shoots, in comparison with normal N supply. However, significant differences were found among the genotypes. The genotypes with high NUE (ZD9 and XZ149) showed higher N concentration, increased number of tillers, improved chlorophyll and soluble proteins in both roots and shoots as compared to the inefficient ones (HXRL and XZ56). Furthermore, nitrate transporter gene (NRT2.1) showed higher expression under low N, both in roots and leaves of N efficient genotypes, as compared to the N inefficient ones. However, N assimilatory genes (GS1 and GS2) showed higher expression under normal and low N level, in leaves and roots respectively. The outcome of the study revealed that genotypes with higher NUE (ZD9 and XZ149) performed better under reduced N supply, and may require relatively less N fertilizer for normal growth and development, as compared to those with lower NUE. The study also revealed a time-specific expression pattern of studied genes, indicating the duration of low N stress. The current study suggested that future work must involve the time course as a key factor while studying expression patterns of these genes to better understand the genetic basis of low-N tolerance.

Successful Use of Deltopectoral Flap in Reconstruction of Defect Caused by Squamous Cell Carcinoma.

Deltopectoral flap is a widely used flap in reconstruction surgery. A patient presented with extra-oral solitary swelling on the right lower jaw and an intra-oral exophytic growth located along the lower border of right mandibular jaw. Incisional biopsy was done which revealed moderately-differentiated squamous cell carcinoma. Clinical staging was T4N1M0. Treatment plan devised was segmental mandibulectomy along with excision of involved skin, supraomohyoid neck dissection followed by reconstruction. Apron incision with lip split was used. The defect caused by the resection was closed using deltopectoral flap. Deltopectoral flap was preferred for reconstruction as it is convenient for patients with low socio- economic status and for hospitals with less technical facilities. It can easily be raised from anterior chest area because of its pliability. This case report highlights the role of deltopectoral flap as an alternate to free flap for reconstruction.

Order and disorder in the domain organization of the plasmid partition protein KorB.

The plasmid partition protein KorB has a dual role: it is essential for the correct segregation of the low copy number broad host range RK2 plasmid while also being an important regulator of transcription. KorB belongs to the ParB family of proteins, and partitioning in RK2 has been studied as a simplified model of bacterial chromosome segregation. Structural information on full-length ParB proteins is limited, mainly due to the inability to grow crystals suitable for diffraction studies. We show, using CD and NMR, that KorB has regions of significant intrinsic disorder and hence it adopts a multiplicity of conformations in solution. The biophysical data are consistent with bioinformatic predictions based on the amino acid sequence that the N-terminal region and also the region between the central DNA-binding domain and the C-terminal dimerization domain are intrinsically disordered. We have used small angle x-ray scattering data to determine the ensemble of solution conformations for KorB and selected deletion mutants, based on models of the known domain structures. This conformational range of KorB is likely to be biologically required for DNA partitioning and for binding to a diverse set of partner proteins.

A single aromatic residue in transcriptional repressor protein KorA is critical for cooperativity with its co-regulator KorB.

A central feature of broad host range IncP-1 plasmids is the set of regulatory circuits that tightly control plasmid core functions under steady-state conditions. Cooperativity between KorB and either KorA or TrbA repressor proteins is a key element of these circuits and deletion analysis has implicated the conserved C-terminal domain of KorA and TrbA in this interaction. By NMR we show that KorA and KorB interact directly and identify KorA amino acids that are affected on KorB binding. Studies on mutants showed that tyrosine 84 (or phenylalanine, in some alleles) is dispensable for repressor activity but critical for the specific interaction with KorB in both in vivo reporter gene assays and in vitro electrophoretic mobility shift and co-purification assays. This confirms that direct and specific protein-protein interactions are responsible for the cooperativity observed between KorB and its corepressors and lays the basis for determining the biological importance of this cooperativity.

Distribution of the partitioning protein KorB on the genome of IncP-1 plasmid RK2.

The ParB family partitioning protein, KorB, of plasmid RK2 is central to a regulatory network coordinating replication, maintenance and transfer genes. Previous immunofluorescence microscopy indicated that the majority of KorB is localized in plasmid foci. The 12 identified KorB binding sites on RK2 are differentiated by: position relative to promoters; binding strength; and cooperativity with other repressors and so the distribution of KorB may be sequestered around a sub-set of sites. However, chromatin immunoprecipitation analysis showed that while RK2 DNA molecules appear to sequester KorB to create a higher local concentration, cooperativity between DNA binding proteins does not result in major differences in binding site occupancy. Thus under steady state conditions all operators are close to fully occupied and this correlates with gene expression on the plasmid being highly repressed.