Enabling High Reversibility of Zn anode via Interfacial Engineering Induced by Amino acid Electrolyte Additive.

Despite possessing substantial benefits of enhanced safety and cost-effectiveness, the aqueous zinc ion batteries (AZIBs) still suffers with the critical challenges induced by inherent instability of Zn metal in aqueous electrolytes. Zn dendrites, surface passivation, and corrosion are some of the key challenges governed by water-driven side reactions in Zn anodes. Herein, a highly reversible Zn anode is demonstrated via interfacial engineering of Zn/electrolyte driven by amino acid D-Phenylalanine (DPA) additions. The preferential adsorption of DPA and the development of compact SEI on the Zn anode suppressed the side reactions, leading to controlled and uniform Zn deposition. As a result, DPA added aqueous electrolyte stabilized Zn anode under severe test environments of 20.0 mA cm-2 and 10.0 mAh cm-2 along with an average plating/stripping Coulombic efficiency of 99.37%. Under multiple testing conditions, the DPA-incorporated electrolyte outperforms the control group electrolyte, revealing the critical additive impact on Zn anode stability. This study advances interfacial engineering through versatile electrolyte additive(s) toward development of stable Zn anode, which may lead to its practical implementation in aqueous rechargeable zinc batteries.

Clinical and genetic investigation of 14 families with various forms of short stature syndromes.

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.

An Expedient Approach to Access Phenalenones via Unconventional [1,2]-Phospha-Brook Rearrangement/Carbonyl Migration.

An efficient protocol for the synthesis of 2,3-disubstituted phenalenones from para-quinone methides (p-QMs) and acenaphthoquinone is described. The reaction involves P(NMe2)3-mediated [1,2]-phospha-Brook rearrangement followed by Lewis acid-assisted 1,2-carbonyl migration to afford the 2,3-disubstituted phenalenones. The developed protocol tolerates a broad range of substrates to form a variety of phenalenones in good to excellent yields. Moreover, the utility of the synthesized phenalenones is also demonstrated by performing its transformations to other adducts.

Applicability of SCoT markers in unraveling genetic variation and population structure among sugar beet (Beta vulgaris L.) germplasm.

BACKGROUND: Sugar beet (Beta vulgaris L.) holds significant importance as a crop globally cultivated for sugar production. The genetic diversity present in sugar beet accessions plays a crucial role in crop improvement programs. METHODS AND RESULTS: During the present study, we collected 96 sugar beet accessions from different regions and extracted DNA from their leaves. Genomic DNA was amplified using SCoT primers, and the resulting fragments were separated by gel electrophoresis. The data were analyzed using various genetic diversity indices, and constructed a population STRUCTURE, applied the unweighted pair-group method with arithmetic mean (UPGMA), and conducted Principle Coordinate Analysis (PCoA). The results revealed a high level of genetic diversity among the sugar beet accessions, with 265 bands produced by the 10 SCoT primers used. The percentage of polymorphic bands was 97.60%, indicating substantial genetic variation. The study uncovered significant genetic variation, leading to higher values for overall gene diversity (0.21), genetic distance (0.517), number of effective alleles (1.36), Shannon's information index (0.33), and polymorphism information contents (0.239). The analysis of molecular variance suggested a considerable amount of genetic variation, with 89% existing within the population. Using STRUCTURE and UPGMA analysis, the sugar beet germplasm was divided into two major populations. Structure analysis partitioned the germplasm based on the origin and domestication history of sugar beet, resulting in neighboring countries clustering together. CONCLUSION: The utilization of SCoT markers unveiled a noteworthy degree of genetic variation within the sugar beet germplasm in this study. These findings can be used in future breeding programs with the objective of enhancing both sugar beet yield and quality.

Simultaneous removal of ammonia nitrogen, phosphate, zinc, and phenol by degradation of cellulose in composite mycelial pellet bioreactor: Enhanced performance and community co-assembly mechanism.

In this experiment, the prepared tea biochar-cellulose@LDH material (TB-CL@LDH) was combined with mycelium pellets to form the composite mycelial pellets (CMP), then assembled and immobilized with strains Pseudomonas sp. Y1 and Cupriavidus sp. ZY7 to construct a bioreactor. At the best operating parameters, the initial concentrations of phosphate (PO43--P), ammonia nitrogen (NH4+-N), chemical oxygen demand (COD), zinc (Zn2+), and phenol were 22.3, 25.0, 763.8, 1.0, and 1.0 mg L-1, the corresponding removal efficiencies were 80.4, 87.0, 83.4, 91.8, and 96.6%, respectively. Various characterization analyses demonstrated that the strain Y1 used the additional carbon source produced by the strain ZY7 degradation of cellulose to enhance the removal of composite pollutants and clarified the principle of Zn2+ and PO43--P removal by adsorption, co-precipitation and biomineralization. Pseudomonas and Cupriavidus were the dominant genera according to the high-throughput sequencing. As shown by KEGG results, nitrification and denitrification genes were affected by phenol. The study offers prospects for the simultaneous removal of complex pollutants consisting of NH4+-N, PO43--P, Zn2+, and phenol.

Denitrification driven by additional ferrous (Fe2+) and manganous (Mn2+) and removal mechanism of tetracycline and cadmium (Cd2+) by biogenic Fe-Mn oxides.

Zoogloea sp. MFQ7 achieved excellent denitrification of 91.71% at ferrous to manganous ratio (Fe/Mn) of 3:7, pH of 6.5, nitrate concentration of 25 mg L-1 and carbon to nitrogen ratio of 1.5. As the Fe/Mn ratio increasd, the efficiency of nitrate removal gradually decreased, indicating that strain MFQ7 had a higher affinity for Mn2+ than Fe2+. In situ generated biogenic Fe-Mn oxides (BFMO) contained many iron-manganese oxides (MnO2, Mn3O4, FeO(OH), Fe2O3, and Fe3O4) as well as reactive functional groups, which play an significant part in tetracycline (TC) and cadmium (Cd2+) adsorption. The adsorption of TC and Cd2+ by BFMO can better fit the pseudo-second-order and Langmuir models. In addition, multiple characterization results of before and after adsorption indicated that the removal mechanism of BFMO on TC and Cd2+ was probably surface complexation adsorption and redox reactions.

Fully Endoscopic Retrosigmoid Approach for Cerebellopontine Angle Tumors.

BACKGROUND: Fully endoscopic or endoscope-controlled approaches are essentially keyhole approaches in which rigid endoscopes are the sole visualization tools used during the whole procedure. At the early attempts of endoscope-assisted cranial surgery, it was noted that rigid endoscopes enabled overcoming the problem of suboptimal visualization when small exposures are used. The technical specifications and design of the currently available rigid endoscopes are associated with a group of unique features that define the endoscopic view and lay the basis for its superiority over the microscopic view during brain surgery. Fully endoscopic retrosigmoid approach for cerebellopontine angle tumors is a minimally invasive approach that is not routinely practiced by neurosurgeons, with few series published so far. Unfamiliarity with the technique, steep learning curve, and concerns about inadequate exposure, neurovascular injury, and decreased visibility may explain this fact. In this chapter we elaborate on the surgical technique and nuances of the fully endoscopic retrosigmoid approach and present an overview of the published series. METHODS: From a prospective database of endoscopic procedures maintained by the senior author, clinical data, imaging studies, operative charts, and videos of cases undergoing fully endoscopic retrosigmoid approach for cerebellopontine angle tumors were retrieved and analyzed. The pertinent literature was also reviewed. RESULTS: The surgical technique of the fully endoscopic retrosigmoid approach was formulated. CONCLUSION: The endoscopic technique has many advantages over the conventional procedures. In our hands, the technique has proven to be feasible, efficient, and minimally invasive with excellent results.

A Novel Wearable Sensor for Measuring Respiration Continuously and in Real Time.

In this work, a flexible textile-based capacitive respiratory sensor, based on a capacitive sensor structure, that does not require direct skin contact is designed, optimised, and evaluated using both computational modelling and empirical measurements. In the computational study, the geometry of the sensor was examined. This analysis involved observing the capacitance and frequency variations using a cylindrical model that mimicked the human body. Four designs were selected which were then manufactured by screen printing multiple functional layers on top of a polyester/cotton fabric. The printed sensors were characterised to detect the performance against phantoms and impacts from artefacts, normally present whilst wearing the device. A sensor that has an electrode ratio of 1:3:1 (sensor, reflector, and ground) was shown to be the most sensitive design, as it exhibits the highest sensitivity of 6.2% frequency change when exposed to phantoms. To ensure the replicability of the sensors, several batches of identical sensors were developed and tested using the same physical parameters, which resulted in the same percentage frequency change. The sensor was further tested on volunteers, showing that the sensor measures respiration with 98.68% accuracy compared to manual breath counting.

Mechanisms of ammonia, calcium and heavy metal removal from nutrient-poor water by Acinetobacter calcoaceticus strain HM12.

An Acinetobacter calcoaceticus strain HM12 capable of heterotrophic nitrification-aerobic denitrification (HN-AD) under nutrient-poor conditions was isolated, with an ammonia nitrogen (NH4+-N) removal efficiency of 98.53%. It can also remove heavy metals by microbial induced calcium precipitation (MICP) with a Ca2+ removal efficiency of 75.91%. Optimal conditions for HN-AD and mineralization of the strain were determined by kinetic analysis (pH = 7, C/N = 2.0, Ca2+ = 70.0 mg L-1, NH4+-N = 5.0 mg L-1). Growth curves and nitrogen balance elucidated nitrogen degradation pathways capable of converting NH4+-N to gaseous nitrogen. The analysis of the bioprecipitation showed that Zn2+ and Cd2+ were removed by the MICP process through co-precipitation and adsorption (maximum removal efficiencies of 93.39% and 80.70%, respectively), mainly ZnCO3, CdCO3, ZnHPO4, Zn3(PO4)2 and Cd3(PO4)2. Strain HM12 produces humic and fulvic acids to counteract the toxicity of pollutants, as well as aromatic proteins to increase extracellular polymers (EPS) and promote the biomineralization process. This study provides a experimental evidence for the simultaneous removal of multiple pollutants from nutrient-poor waters.

Antimicrobial Properties and Therapeutic Potential of Bioactive Compounds in Nigella sativa: A Review.

Nigella sativa (N. sativa; Ranunculaceae), commonly referred to as black cumin, is one of the most widely used medicinal plants worldwide, with its seeds having numerous applications in the pharmaceutical and food industries. With the emergence of antibiotic resistance in pathogens as an important health challenge, the need for alternative microbe-inhibitory agents is on the rise, whereby black cumin has gained considerable attention from researchers for its strong antimicrobial characteristics owing to its high content in a wide range of bioactive compounds, including thymoquinone, nigellimine, nigellidine, quercetin, and O-cymene. Particularly, thymoquinone increases the levels of antioxidant enzymes that counter oxidative stress in the liver. Additionally, the essential oil in N. sativa seeds effectively inhibits intestinal parasites and shows moderate activity against some bacteria, including Bacillus subtilis and Staphylococcus aureus. Thymoquinone exhibits minimum inhibitory concentrations (MICs) of 8-16 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA) and exhibits MIC 0.25 µg/mL against drug-resistant mycobacteria. Similarly, quercetin shows a MIC of 2 mg/mL against oral pathogens, such as Streptococcus mutans and Lactobacillus acidophilus. Furthermore, endophytic fungi isolated from N. sativa have demonstrated antibacterial activity. Therefore, N. sativa is a valuable medicinal plant with potential for medicinal and food-related applications. In-depth exploration of the corresponding therapeutic potential and scope of industrial application warrants further research.

The Effect of Molecular Structure on the Properties of Fluorene Derivatives for OLED Applications.

A new family of symmetrical fluorene derivatives with different types of substituents attached to the C-2 and C-7 positions of the fluorene core synthesized by the Sonogashira coupling reactions is reported. The electronic structures and the properties of the compounds investigated by means of photoelectron emission spectroscopy, UV-Vis absorption and photoluminescent spectroscopy as well as by DFT and TD-DFT theoretical calculations are discussed. It is shown that the nature of substituents influences the π-conjugation of the molecules. No intermolecular charge transfer within the investigated wavelength range is observed. The applicability of the synthesized compounds in organic light-emitting diodes (OLEDs) based on exciplex emission is demonstrated. The advanced co-deposition technique with the tuned OLED architecture was applied and resulted in improved OLED parameters.

Deciphering fungicide resistance in Phytophthora: mechanisms, prevalence, and sustainable management approaches.

The genus Phytophthora contains more than 100 plant pathogenic species that parasitize a wide range of plants, including economically important fruits, vegetables, cereals, and forest trees, causing significant losses. Global agriculture is seriously threatened by fungicide resistance in Phytophthora species, which makes it imperative to fully comprehend the mechanisms, frequency, and non-chemical management techniques related to resistance mutations. The mechanisms behind fungicide resistance, such as target-site mutations, efflux pump overexpression, overexpression of target genes and metabolic detoxification routes for fungicides routinely used against Phytophthora species, are thoroughly examined in this review. Additionally, it assesses the frequency of resistance mutations in various Phytophthora species and geographical areas, emphasizing the rise of strains that are resistant to multiple drugs. The effectiveness of non-chemical management techniques, including biological control, host resistance, integrated pest management plans, and cultural practices, in reducing fungicide resistance is also thoroughly evaluated. The study provides important insights for future research and the development of sustainable disease management strategies to counter fungicide resistance in Phytophthora species by synthesizing current information and identifying knowledge gaps.

RNA interference: a promising biotechnological approach to combat plant pathogens, mechanism and future prospects.

Plant pathogens and other biological pests represent significant obstacles to crop Protection worldwide. Even though there are many effective conventional methods for controlling plant diseases, new methods that are also effective, environmentally safe, and cost-effective are required. While plant breeding has traditionally been used to manipulate the plant genome to develop resistant cultivars for controlling plant diseases, the emergence of genetic engineering has introduced a completely new approach to render plants resistant to bacteria, nematodes, fungi, and viruses. The RNA interference (RNAi) approach has recently emerged as a potentially useful tool for mitigating the inherent risks associated with the development of conventional transgenics. These risks include the use of specific transgenes, gene control sequences, or marker genes. Utilizing RNAi to silence certain genes is a promising solution to this dilemma as disease-resistant transgenic plants can be generated within a legislative structure. Recent investigations have shown that using target double stranded RNAs via an effective vector system can produce significant silencing effects. Both dsRNA-containing crop sprays and transgenic plants carrying RNAi vectors have proven effective in controlling plant diseases that threaten commercially significant crop species. This article discusses the methods and applications of the most recent RNAi technology for reducing plant diseases to ensure sustainable agricultural yields.

Innovative strategies for characterizing and managing huanglongbing in citrus.

Huanglongbing is a severe citrus disease that causes significant tree and crop losses worldwide. It is caused by three Candidatus liberibacter species and spread by psyllids and infected budwood. Various methods have been used to diagnose and understand HLB, including recent advances in molecular and biochemical assays that explore the pathogen's mode of action and its impact on the host plant. Characterization is essential for developing sustainable HLB management strategies. Nanotechnology, particularly nano sensors and metal nanoparticles, shows potential for precise disease diagnosis and control. Additionally, antibiotics, nanomaterials, and genetic engineering techniques like transgenesis offer promising avenues for mitigating HLB. These diverse approaches, from conventional to cutting-edge, contribute to developing integrated HLB management strategies for sustainable citrus cultivation. The review highlights the significant advancements in conventional and advanced molecular and biochemical characterization of HLB, aiding in early detection and understanding of the infection mechanism. It emphasizes the multidimensional efforts required to characterize disease and devise innovative management strategies. As the citrus industry faces unprecedented challenges, exploring new frontiers in HLB research provides hope for sustainable solutions and a resilient future for global citrus cultivation.

Effect of haemodialysis practice guideline on dialysis indicators and haemodynamic complications among patients undergoing haemodialysis.

To assess the effect of haemodialysis practice guidelines on dialysis indicators and haemodynamic complications, the comparative study was conducted at the dialysis unit of Sheikh Zayed Hospital, Lahore, Pakistan, and comprised patients undergoing haemodialysis who were divided into intervention group A in which updated haemodialysis practice guidelines were used, and control group B in which routine base dialysis was given. Data was collected using a self-structured tool. Data was analysed using McNemar test and Mann-Whitney U-test with p<0.05. Compared to baseline, there was a significant improvement in post-intervention ratio of effective removal of clearance (K) resulting from the treatment characterised by time (t) in the patient with a specific volume of distribution (V), or Kt/V, median & IQR 0.83(0.355) vs 1.21(0.11) and percentage of urea reduction ratio with median & IQR 49(12) vs. 66.5(18.65) (p<0.05). Intradialytic hypotension was found in 17(56.6%) subjects in group B and in 4(13.4%) in group A (p=0.002). Intradialytic hypertension was found in 8(25.6%) patients in group B and 1(3.4%) in group A (p=0.039). It is recommended that dialysis be performed in accordance with the most recent clinical guidelines in order to improve practices and to increase haemodialysis effectiveness.

Hydrophilic Cocrystals with Water Switched Luminescence.

Utilizing water molecules to regulate the luminescence properties of solid materials is highly challenging. Herein, we develop a strategy to produce water-triggered luminescence-switching cocrystals by coassembling hydrophilic donors with electron-deficient acceptors, where 1,2,4,5-Tetracyanobenzene (TCNB) was used as the electron acceptor and pyridyl benzimidazole derivatives were used as the electron donors enabling multiple hydrogen-bonds. Two cocrystals, namely 2PYTC and 4PYTC were obtained and showed heat-activated emission, and such emission could be quenched or weakened by adding water molecules. The cocrystal structure exhibited the donor molecule that can form multiple hydro bonds with water and acceptor molecules due to the many nitrogen atoms of them. The analyses of the photophysical data, powder X-ray diffraction, and other data confirmed the reversible fluorescence "on-off" effects were caused by eliminating and adding water molecules in the crystal lattice. The density functional theory calculations indicate that the vibration of the O-H bond of water molecules in the cocrystal can absorb the excitation energy and suppress fluorescence. Furthermore, the obtained cocrystals also showed temperature, humidity, and H+ /NH4 + responsive emission behavior, which allows their applications as thermal and humidity sensors, and multiple information encryptions. This research paves the way for preparing intelligent hydrophilic organic cocrystal luminescent materials.

Host AKT-mediated phosphorylation of HIV-1 accessory protein Vif potentiates infectivity via enhanced degradation of the restriction factor APOBEC3G.

HIV-1 encodes accessory proteins that neutralize antiviral restriction factors to ensure its successful replication. One accessory protein, the HIV-1 viral infectivity factor (Vif), is known to promote ubiquitination and proteasomal degradation of the antiviral restriction factor apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G), a cytosine deaminase that leads to hypermutations in the viral DNA and subsequent aberrant viral replication. We have previously demonstrated that the HIV-1 viral transcription mediator Tat activates the host progrowth PI-3-AKT pathway, which in turn promotes HIV-1 replication. Because the HIV-1 Vif protein contains the putative AKT phosphorylation motif RMRINT, here we investigated whether AKT directly phosphorylates HIV-1 Vif to regulate its function. Coimmunoprecipitation experiments showed that AKT and Vif interact with each other, supporting this hypothesis. Using in vitro kinase assays, we further showed that AKT phosphorylates Vif at threonine 20, which promotes its stability, as Vif becomes destabilized after this residue is mutated to alanine. Moreover, expression of dominant-negative kinase-deficient AKT as well as treatment with a chemical inhibitor of AKT increased K48-ubiquitination and proteasomal degradation of HIV-1 Vif. In contrast, constitutively active AKT (Myr-AKT) reduced K48-ubiquitination of Vif to promote its stability. Finally, inhibition of AKT function restored APOBEC3G levels, which subsequently reduced HIV-1 infectivity. Thus, our results establish a novel mechanism of HIV-1 Vif stabilization through AKT-mediated phosphorylation at threonine 20, which reduces APOBEC3G levels and potentiates HIV-1 infectivity.

Genomic characterization and comparative genomic analysis of HS-associated Pasteurella multocida serotype B:2 strains from Pakistan.

BACKGROUND: Haemorrhagic septicaemia (HS) is a highly fatal and predominant disease in livestock, particularly cattle and buffalo in the tropical regions of the world. Pasteurella multocida (P. multocida), serotypes B:2 and E:2, are reported to be the main causes of HS wherein serotype B:2 is more common in Asian countries including Pakistan and costs heavy financial losses every year. As yet, very little molecular and genomic information related to the HS-associated serotypes of P. multocida isolated from Pakistan is available. Therefore, this study aimed to explore the characteristics of novel bovine isolates of P. multocida serotype B:2 at the genomic level and perform comparative genomic analysis of various P. multocida strains from Pakistan to better understand the genetic basis of pathogenesis and virulence. RESULTS: To understand the genomic variability and pathogenomics, we characterized three HS-associated P. multocida serotype B:2 strains isolated from the Faisalabad (PM1), Peshawar (PM2) and Okara (PM3) districts of Punjab, Pakistan. Together with the other nine publicly available Pakistani-origin P. multocida strains and a reference strain Pm70, a comparative genomic analysis was performed. The sequenced strains were characterized as serotype B and belong to ST-122. The strains contain no plasmids; however, each strain contains at least two complete prophages. The pan-genome analysis revealed a higher number of core genes indicating a close resemblance to the studied genomes and very few genes (1%) of the core genome serve as a part of virulence, disease, and defense mechanisms. We further identified that studied P. multocida B:2 strains harbor common antibiotic resistance genes, specifically PBP3 and EF-Tu. Remarkably, the distribution of virulence factors revealed that OmpH and plpE were not present in any P. multocida B:2 strains while the presence of these antigens was reported uniformly in all serotypes of P. multocida. CONCLUSION: This study's findings indicate the absence of OmpH and PlpE in the analyzed P. multocida B:2 strains, which are known surface antigens and provide protective immunity against P. multocida infection. The availability of additional genomic data on P. multocida B:2 strains from Pakistan will facilitate the development of localized therapeutic agents and rapid diagnostic tools specifically targeting HS-associated P. multocida B:2 strains.

Employing computational tools to design a multi-epitope vaccine targeting human immunodeficiency virus-1 (HIV-1).

BACKGROUND: Despite being in the 21st century, the world has still not been able to vanquish the global AIDS epidemic, and the only foreseeable solution seems to be a safe and effective vaccine. Unfortunately, vaccine trials so far have returned unfruitful results, possibly due to their inability to induce effective cellular, humoral and innate immune responses. The current study aims to tackle these limitations and propose the desired vaccine utilizing immunoinformatic approaches that have returned promising results in designing vaccines against various rapidly mutating organisms. For this, all polyprotein and protein sequences of HIV-1 were retrieved from the LANL (Los Alamos National Laboratory) database. The consensus sequence was generated after alignment and used to predict epitopes. Conserved, antigenic, non-allergenic, T-cell inducing, B-cell inducing, IFN-É£ inducing, non-human homologous epitopes were selected and combined to propose two vaccine constructs i.e., HIV-1a (without adjuvant) and HIV-1b (with adjuvant). RESULTS: HIV-1a and HIV-1b were subjected to antigenicity, allergenicity, structural quality analysis, immune simulations, and MD (molecular dynamics) simulations. Both proposed multi-epitope vaccines were found to be antigenic, non-allergenic, stable, and induce cellular, humoral, and innate immune responses. TLR-3 docking and in-silico cloning of both constructs were also performed. CONCLUSION: Our results indicate HIV-1b to be more promising than HIV-1a; experimental validations can confirm the efficacy and safety of both constructs and in-vivo efficacy in animal models.

Sequence variants in different genes underlying Bardet-Biedl syndrome in four consanguineous families.

BACKGROUND: Bardet-Biedl Syndrome (BBS) is a rare (1:13,500-1-160,000) heterogeneous congenital disorder, characterized by postaxial polydactyly, obesity, hypogonadism, rod-cone dystrophy, cognitive impairment, and renal abnormalities (renal cystic dysplasia, anatomical malformation). To date about twenty-five genes have been identified to cause BBS, which accounts for about 80% of BBS diagnosis. METHODS: In the current study, we have performed mutational screening of four Pakistani consanguineous families (A-D) with clinical manifestation of BBS by microsatellite-based genotyping and whole exome sequencing. RESULTS: Analysis of the data revealed four variants, including a novel/unique inheritance pattern of compound heterozygous variants, p.(Ser40*) and p.(Thr259Leufs*21), in MKKS gene, novel homozygous variant, p.(Gly251Val)] in BBS7 gene and two previously reported p.(Thr259Leufs*21) in MKKS and p.(Met1Lys) in BBS5 gene. The variants were found segregated with the disorder within the families. CONCLUSION: The study not only expanded mutations spectrum in the BBS genes, but this will facilitate diagnosis and genetic counselling of families carrying BBS related phenotypes in Pakistani population.