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Nawaz, M.

Publications and source records attributed to Nawaz, M..

8 recordsLinked to original sources

Ancient DNA reveals matrilineal organisation and recurrent unions between dominant matrilines in Iron Age Britain

Kinship practices underpin all traditional societies, forming the basis for socially sanctioned reproductive unions, residence patterns and the inheritance of rights and property1,2. Although the relationship between biological relatedness and kinship is not always straightforward, ancient DNA studies are increasingly used to examine the extent to which biological relatedness underpinned social constructs of kinship in prehistoric societies3-6. Here, we report the analysis of genome-wide data for 534 individuals from the Arras Culture of Middle Iron Age northeast England (including 390 from Wetwang Slack, 100 from Pocklington, and 29 from Melton), finding evidence for communities with kinship systems structured along matrilineal lines. At Wetwang Slack, we reconstruct a 13-generation pedigree comprising 195 individuals structured around female-line connections: matrilineal transmissions greatly outnumbered patrilineal ones and male reproductive partners were largely absent from the cemetery, plausibly because they were buried in their own natal communities. Furthermore, the three main sites with robust sample sizes were characterised by non-overlapping dominant mitochondrial haplogroups, implying a maternal clan-based structure. Reproductive unions at Wetwang Slack suggest a recurrent alliance between two dominant maternal descent groups, with members of each group never reproducing with members of their own maternal lineage. Meanwhile, three individuals from lavishly furnished chariot burials at Wetwang Slack were close maternal relatives belonging to a lineage with consecutive generations of close kin unions, a pattern largely absent among other individuals at the site. These results indicate highly distinctive social practices among an elite group embedded in the wider kinship network of the Arras community.

genetics↗

Buried in two places: Lineages from elite Maya tombs also found in distant caves

Classic Maya societies (250-900 CE) carved out urban centers in the rainforest reaching population heights and political complexity previously unknown in the Mesoamerican tropics. Kinship was a central feature of the social fabric, and rulership was legitimized through claims of direct descent from mythical ancestors. Mortuary practices kept the dead close to the living, and ancestor veneration sometimes produced complex deposits of disarticulated remains that are difficult to identify and whose biological relationships to one another cannot be understood without genetic data. We screened 487 human tooth and bone samples and successfully generated genome-wide data for 430 of them. Of these, 341 samples representing 107 distinct individuals were recovered from both elite and non-elite tombs in a Classic period kingdom (250-900) CE in the rugged Maya Mountains of Belize. Remarkably, 24 of these individuals have skeletal elements in both an elite tomb and in a ritual tooth cache in a distant cave located 26.5km away on the other side of the Maya Mountains. These results indicate that elite lineages created ancestors from their deceased relatives in geographically expansive ways and highlights the importance of caves in the belief system of Classic Maya elites.

genetics↗

Subsistence transition preceded population turnover in the eastern Colombian Andes

Northwest South America was a pivotal region for human dispersals and cultural exchange during the Holocene. The Altiplano Cundiboyacense, a high-altitude plateau in the Eastern Cordillera of the Northern Andes of Colombia, preserves one of the most continuous archaeological sequences in the Americas, spanning from late Pleistocene hunter-gatherer groups to final late Holocene Muisca chiefdoms. Increasing the regional ancient DNA sample size 11-fold, we report genome-wide data from 209 individuals who lived over a period of more than 7000 years. This includes hunter-gatherers from the early-middle (10,000-7000 BP) and middle (7000-4000 BP) Holocene, initial late Holocene people (4000-2500 BP) who have the first isotopic evidence of C-enriched diets (attributed to maize), and populations associated with increasing sedentism and food production in the Herrera (2200-1300 BP) and Muisca (1200-500 BP) Periods. Previous work identified a major population turnover distinguishing earlier groups from Herrera-Muisca Period populations, but the absence of individuals dating 6000-2000 BP in that study left unresolved whether this ancestry shift was gradual or abrupt and whether it accompanied the earliest isotopic evidence of dietary input from maize or coincided with the later emergence of Herrera culture. We show that individuals predating the Herrera Period form a lineage that persisted for over five millennia, with population structure driven by drift in small groups and no detectable external gene flow. Two individuals who lived [~]2800 years ago - one directly dated to 983-835 calBCE - exhibit genetic profiles entirely consistent with hunter-gatherer ancestry yet have isotopic values consistent with the incorporation of maize into their diets, indicating subsistence change without population replacement. The emergence of Herrera culture [~]2200 BP coincided with a sharp genetic break, reflecting the migration of people carrying ancestry diverged by up to ten millennia into the Sabana de Bogota and displacing previously established peoples. By co-analyzing ancient data with modern Native Americans, we show these later populations derived from a mixture [~]4000 years ago of groups related to Chibchan language speakers of lower Central America and ones related to present-day people at the Amazonian-Andean interface who may have lived along the Chibchan expansion route. In the Herrera and Muisca Periods, genetic substructure distinguishes people from the southern and northern Altiplano, consistent with the cultural differentiation of these regions in the archaeological record. IN BRIEFAncient DNA data from the eastern Colombian Andes reveal five millennia of population continuity during which C plants were incorporated into subsistence systems without population replacement, followed later by a major ancestry turnover involving a population with ancestry admixed between that found in Chibchan-related groups and at the Amazonian-Andean interface.

genetics↗

Targeted delivery of mRNA to the heart via extracellular vesicles or lipid nanoparticles

Targeted mRNA transport plays a crucial role in enhancing the therapeutic efficacy of the molecule, reducing its side effects, and minimizing off-target effects. Systemic administration of mRNA through lipid nanoparticles (LNPs) or extracellular vesicles (EVs) predominantly results in mRNA accumulation in the liver. We hypothesized that cardiac-specific EVs could more effectively target the transport of mRNA to the heart, in comparison to non-cardiac-specific EVs or LNPs. In mice, after intravenous administration, EVs from cardiac progenitor cells (CPC-EVs) were the most efficient to transport the modified mRNA, encoding vascular endothelial growth factor A (VEGF-A), to mouse heart, with minimal liver accumulation compared to non-cardiac-specific EVs or LNPs. Additionally, intracardiac injections of CPC-EVs not only demonstrate that they are the most adapted vehicle for interacting with heart tissue, delivering the mRNA to cells, and inducing maximal VEGF-A protein production, but RNA-seq analyses also revealed their minimal impact on overall gene expression, compared to LNPs or non-cardiac-specific EVs. Furthermore, immunofluorescence staining of CD31 and -SMA, markers of microvascular density, showed increased vessel density in mouse aortic rings following the delivery of VEGF-A mRNA via CPC-EVs. These findings suggest that CPC-EVs are superior in mRNA targeting to heart, communication with cardiac cells, and causing minimal transcriptomic changes during VEGF-A mRNA delivery. Therefore, CPC-EVs could be promising vectors for heart-targeted mRNA delivery, potentially reducing liver accumulation.

molecular biology↗

Integration of RT-LAMP and Microfluidic Technology for Detection of SARS-CoV-2 in Wastewater as an Advanced Point-of-care Platform

Development of lab-on-a-chip (LOC) system based on integration of reverse transcription loop-mediated isothermal amplification (RT-LAMP) and microfluidic technology is expected to speed up SARS-CoV-2 diagnostics allowing early intervention. In the current work, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and RT-LAMP assays were performed on extracted RNA of 7 wastewater samples from COVID-19 hotspots. RT{square}LAMP assay was also performed on wastewater samples without RNA extraction. Current detection of SARS-CoV-2 is mainly by RT-qPCR of ORF (ORF1ab) and N genes so we targeted both to find the best surrogate marker for SARS-CoV-2 detection. We also performed RT-LAMP with/without RNA extraction inside microfluidic device to target both genes. Positivity rates of RT-qPCR and RT-LAMP performed on extracted RNA were 100.0% (7/7) and 85.7% (6/7), respectively. RT-qPCR results revealed that all 7 wastewater samples were positive for N gene (Ct range 37-39), and negative for ORF1ab, suggesting that N gene could be used as a surrogate marker for detection of SARS-CoV-2. RT-LAMP of N and ORF (ORF1a) genes performed on wastewater samples without RNA extraction indicated that all 7 samples remains pink (negative). The color remains pink in all microchannels except microchannels which subjected to RT-LAMP for targeting N region after RNA extraction (yellow color) in 6 out of 7 samples. This study shows that SARS-CoV-2 was successfully detected from wastewater samples using RT-LAMP in microfluidic chips.

microbiology↗

The Role of Action Potential Waveform in Failure of Excitation Contraction Coupling

Excitation contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, ICU acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+ is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a range of several mV of resting potential. While some studies have hypothesized the sudden failure of ECC is due to all-or-none failure of excitation, other studies suggest failure of excitation is graded. Intracellular recordings of action potentials (APs) in individual fibers during depolarization revealed that APs do not fail in an all-or-none manner. Simultaneous imaging of Ca2+ transients during depolarization revealed failure over a narrow range of resting potentials. An AP property that closely correlated with the sudden failure of the Ca2+ transient was the integral of AP voltage with respect to time. We hypothesize the close correlation is due to the combined dependence on time and voltage of Ca2+ release from the sarcoplasmic reticulum. The quantitative relationships established between resting potential, APs and Ca2+ transients provide the foundation for future studies of depolarization-induced failure of ECC in diseases such as periodic paralysis.

physiology↗

An assessment of efficacy of Iodine complex (Renessans) against SARS-CoV-2 in non-human primates (Rhesus macaque)

Renessans is an iodine complex which has proven in vitro antiviral activity including Anti-SARS-CoV-2 activity. The present study was designed to determine its efficacy against SARS-CoV-2 in monkeys (Rhesus macaque). A total of 14 monkeys were divided into four groups: A) Prophylactic group (n=03), (B) Treatment group (n=03), (C) infection control group (n=04) and (D) negative control group (n=04) and were housed in BSL-3 Animal facility while group D was housed at another animal house. Group A was administered with Renessans @ 2.85 mg/7 kg from 5 days prior to the infection to 08 days post infections (DPI). Group B was administered with Renessans from 03-08 DPI @ 2.85 mg/7 kg. Group C was administered with WIF only. The infection @ 2 x 106 TCID of SARS-CoV-2 was given to all group monkeys through intranasal and oral route under anesthesia. Nasal swab samples (at different times) and fecal matter on daily basis were collected for the detection of SARS-CoV-2 through real-time quantitative PCR. Three monkeys (one from each of group A, B and C) were euthanized at 07 DPI to determine the gross pathological lesions and SARS-CoV-2 detection from internal tissues. Nasal swabs from all the monkeys from group A, B and C were positive for SARS-CoV-2 at 02 and 07 DPI (Day 05 of treatment). At 14 DPI, all (100%) nasal swabs from group A were negative for SARS-CoV-2 while 50% and 100% were positive from group B and C, respectively. At 21 DPI, monkeys from group B were negative and all in group C were still positive for SARS-CoV-2. Similarly, fecal matter of monkeys in group A and B was returned negative in significantly lesser time as compared to monkeys from infection control group. Based on these research findings it is concluded that the Renessans has in-vivo SARS-CoV-2 activity and may result in early clearance of SARS-CoV-2. Therefore, a clinical trial of the drug in COVID-19 patients may reveal its anti-COVID-19 potential.

microbiology↗

An in vitro assessment of anti-SARS-CoV-2 activity of oral preparations of iodine complexes (RENESSANS)

Since the emergence of CoVID-19 pandemic in China in late 2019, scientists are striving hard to explore non-toxic, viable anti-SARS-CoV-2 compounds or medicines. We determined In Vitro anti-SARS-CoV-2 activity of oral formulations (syrup and capsule) of an Iodine-complex (Renessans). A monolayer of vero cells were exposed to SARS-CoV-2 in the presence and absence of different concentrations (equivalent to 50, 05 and 0.5 g/ml of I2) of Renessans. Anti-SARS-CoV-2 activity of each of the formulation was assessed in the form of cell survival, SARS-CoV-2-specific cytopathic effect (CPE) and genome quantization. With varying concentrations of syrup and capsule, a varying rate of inhibition of CPE, cells survival and virus replication was observed. Compared to 0.5 g/ml concentration of Renessans syrup, 5 and 50 g/ml showed comparable results where there was a 100% cell survival, no CPEs and a negligible viral replication ({Delta}CT= 0.11 and 0.13, respectively). This study indicates that Renessans, containing iodine, may have potential activity against SARS-CoV-2 which needs to be further investigated in human clinical trials.

microbiology↗